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University of Groningen

Self-assembling nanofiber hydrogels to attenuate epithelial mesenchymal transition in lens

epithelial cells

da Cruz Barros, Raquel Sofia

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from

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Publication date:

2018

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

da Cruz Barros, R. S. (2018). Self-assembling nanofiber hydrogels to attenuate epithelial mesenchymal

transition in lens epithelial cells. University of Groningen.

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170

com intervenção mínima com o filme lacrimal da córnea de porco revelou um baixo coeficiente de fricção de 0,011 na solução de glicerina. As moléculas de glicerina presumivelmente ligam-se à água, mucinas e células epiteliais e, com isso, melhoram a película de hidratação e a lubrificação melhora. Usando microscopia confocal, determinamos que a solução de glicerina reduziu o dano nas células epiteliais em 50% em comparação com a solução salina tampão de fosfato.

No capítulo 6 está descrita uma discussão geral sobre a teoria e praticabilidade do trabalho realizado nesta tese. Algumas das melhorias adicionais deste trabalho também foram mencionadas neste capítulo.

P.S. – É extremamente difícil sumariar o meu trabalho em português, porque nunca escrevi (ou descrevi) ciência em português e porque há muitos termos científicos que não são traduzíveis.

171

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Acknowledgements

“Human vocabulary is still not capable, and probably will never be, of knowing, recognizing, and communicating everything that can be humanly experienced and felt.” José Saramago

This PhD and this thesis are only possible mainly due to my supervisors, Theo van Kooten and Henk Busscher. Theo, you are the responsible for me to come to Groningen. With you I learned what is a calm and positive supervisor. You were always there for me. You always supported my decisions and you always gave me the freedom to “think”. I really appreciated that you had always your door open, to clarify my doubts or simply to “brainstorm”. Your positive feedback really boosted my self-esteem. I have learned so much with you and the way you teach. You were also responsible for my love for stainings and microscopy… maybe because we share another passion, photography! Thank you Theo, for your patience, your teachings, comprehension and for being always by my side.

Henk, thank you for making sure that this thesis would be finished. You took an important role in the end of this book. I really appreciate your efforts, even though you really didn’t have to…I had the opportunity to meet with you as a PhD representative and I always admired how fast you could solve problems. Thank you for the time you spent reading this thesis.

Another important person during my PhD was Roel Kuijer, my PCR teacher. Roel, like Theo you always gave me the possibility to share my ideas. And you were always very critical … I really appreciate that! Your critical comments always helped to significantly improve my articles. When I arrived at the BME department, I had a very “depressive” feeling about genetics and PCR in particular. I left with a very positive feeling about it. The reason for it was your patience to teach me, with my own mistakes. For that, but also for your kindness, I thank you.

I also thank the reading committee, prof. dr. Ruud A. Bank, prof. dr. Oliver Stachs and prof. dr. Klaas Nico Faber for the time spent reading this thesis.

This thesis was a truly collaborative work. The work was performed in close collaboration with medical doctors but also with companies. All parties played crucial roles for the success of the project. I have to thank dr. Steven Koopmans and Lisanne Nibourg for all the important inputs, done with an unique, medical perspective. And I also have to thank the people at Nano-FM; Menno de Jong, Edith Gelens, Erna Bulten and Annemarie Tuin. Without you, this thesis could never be finished. I deeply appreciate your efforts to provide me with the crucial biomaterials. You were also always ready to brainstorm, while taking a “warm” cup of coffee. Also, in thank Abbott for its confidence on the project.

Last but not least, I thank Kroon Vlees, for all the porcine materials used in this thesis but also for much more than that… For all the sympathy, and for all the chats while killing time in the slaughterhouse. I would like to thank in particular to Karina for all the kindness.

Before finishing this thesis I started to work at Wellinq. And I need to give a big thanks to everyone there, for receiving me so well at the company. Barry and Sander, thank you

much more than that, for trusting me and giving me the confidence to grow as a R&D. It has been an amazing experience and I am learning a lot from both of you. I also need to thank the fantastic people that work directly with me; Robert Splinter, Rein, Wouter, Wendy, Henk, Jan, Jannes, Azim, Robert, Rudi, Sjoukje, but also Fransisca, Annet and Herma, these amazing ladies. All the people on the workshop and, of course, the “great/huge” R&D team”; Erik, Gert-Jan, Jan Remke, Jeroen and Caroline. Thank you all, for “the good vibes”!!

But most importantly, Mart. You are one of the smartest person I ever met and I feel honored to be able to work with you. It is impossible to describe how much I have learned with you already. Thank you for being my teacher but also my friend. Thank you for your kindness, for your advices and for your time listen my ideas and “problems”. You are an example for me. Thank you for your support and for everything. I will miss you…

I started as a “fresh” portuguese PhD student in the BME department. I was fortunate to meet different people, from different countries and to be able to understand different cultures. This experience changed me forever! In the beginning, it was very difficult for me to “deal” with the dutch culture. But with time, I became more dutch than portuguese… And now I have to say that sometimes it is more difficult for me to understand the portuguese culture than the dutch one!

The department became my second house, mainly in the beginning of the PhD. I saw a lot of people coming and going. But some were always there. I have to give a big thanks to the permanent staff; Willem, Ina, Willy, Ed, Wya, Joop, Gesinda, Corien, Babs, Jelly, Hans, Minnie, Rene D, Betsy, Chris, Prashant, Jelmer, Henny, Patrick and Romana for all the smiles around the department. And a special thanks to Willem for all the chocolates along this PhD!

It was also a pleasure to work with Prashant and Patrick. I specially thank Deepak for sharing the work that we did in one of the chapters in this thesis. Thank you for your enthusiasm and support!

I would like to thank all the colleagues with whom I worked in the department especially, Hilde, Anna, Adhi, Simon, Joana, Niar, Helen, Arina, Song, Bu, Bart, Brian, Vera, Rebecca, René R, Bart, Sara, Brandon, Akshay, Agnieszka, Deepak, Stefan, Steven, Mayeul, Felipe, Qihui, Philip, Ed and JP.

I am lucky enough to call some of these people as friends… when we are abroad our friends become a bit as our family. Thank you my dear Niar, Joana, Anna and Hilde! Thank you so, so much. I could write an acknowledgment section just for you. Without you surviving this PhD would be a (even) bigger challenge! Having you with me in and outside the department made me feel stronger. Thank you my girls!!

Also thank you my dear Helen, Brian, Feifei, Song, Bu, Arina. You made my life in the department easier. Having you around for lunch, dinner (inside or outside the department) much more than that, for trusting me and giving me the confidence to grow as a R&D. It has been an amazing experience and I am learning a lot from both of you. I also need to thank the fantastic people that work directly with me; Robert Splinter, Rein, Wouter, Wendy, Henk, Jan, Jannes, Azim, Robert, Rudi, Sjoukje, but also Fransisca, Annet and Herma, these amazing ladies. All the people on the workshop and, of course, the “great/huge” R&D team”; Erik, Gert-Jan, Jan Remke, Jeroen and Caroline. Thank you all, for “the good vibes”!!

But most importantly, Mart. You are one of the smartest person I ever met and I feel honored to be able to work with you. It is impossible to describe how much I have learned with you already. Thank you for being my teacher but also my friend. Thank you for your kindness, for your advices and for your time listen my ideas and “problems”. You are an example for me. Thank you for your support and for everything. I will miss you…

I started as a “fresh” portuguese PhD student in the BME department. I was fortunate to meet different people, from different countries and to be able to understand different cultures. This experience changed me forever! In the beginning, it was very difficult for me to “deal” with the dutch culture. But with time, I became more dutch than portuguese… And now I have to say that sometimes it is more difficult for me to understand the portuguese culture than the dutch one!

The department became my second house, mainly in the beginning of the PhD. I saw a lot of people coming and going. But some were always there. I have to give a big thanks to the permanent staff; Willem, Ina, Willy, Ed, Wya, Joop, Gesinda, Corien, Babs, Jelly, Hans, Minnie, Rene D, Betsy, Chris, Prashant, Jelmer, Henny, Patrick and Romana for all the smiles around the department. And a special thanks to Willem for all the chocolates along this PhD!

It was also a pleasure to work with Prashant and Patrick. I specially thank Deepak for sharing the work that we did in one of the chapters in this thesis. Thank you for your enthusiasm and support!

I would like to thank all the colleagues with whom I worked in the department especially, Hilde, Anna, Adhi, Simon, Joana, Niar, Helen, Arina, Song, Bu, Bart, Brian, Vera, Rebecca, René R, Bart, Sara, Brandon, Akshay, Agnieszka, Deepak, Stefan, Steven, Mayeul, Felipe, Qihui, Philip, Ed and JP.

I am lucky enough to call some of these people as friends… when we are abroad our friends become a bit as our family. Thank you my dear Niar, Joana, Anna and Hilde! Thank you so, so much. I could write an acknowledgment section just for you. Without you surviving this PhD would be a (even) bigger challenge! Having you with me in and outside the department made me feel stronger. Thank you my girls!!

Also thank you my dear Helen, Brian, Feifei, Song, Bu, Arina. You made my life in the department easier. Having you around for lunch, dinner (inside or outside the department) much more than that, for trusting me and giving me the confidence to grow as a R&D. It has been an amazing experience and I am learning a lot from both of you. I also need to thank the fantastic people that work directly with me; Robert Splinter, Rein, Wouter, Wendy, Henk, Jan, Jannes, Azim, Robert, Rudi, Sjoukje, but also Fransisca, Annet and Herma, these amazing ladies. All the people on the workshop and, of course, the “great/huge” R&D team”; Erik, Gert-Jan, Jan Remke, Jeroen and Caroline. Thank you all, for “the good vibes”!!

But most importantly, Mart. You are one of the smartest person I ever met and I feel honored to be able to work with you. It is impossible to describe how much I have learned with you already. Thank you for being my teacher but also my friend. Thank you for your kindness, for your advices and for your time listen my ideas and “problems”. You are an example for me. Thank you for your support and for everything. I will miss you…

I started as a “fresh” portuguese PhD student in the BME department. I was fortunate to meet different people, from different countries and to be able to understand different cultures. This experience changed me forever! In the beginning, it was very difficult for me to “deal” with the dutch culture. But with time, I became more dutch than portuguese… And now I have to say that sometimes it is more difficult for me to understand the portuguese culture than the dutch one!

The department became my second house, mainly in the beginning of the PhD. I saw a lot of people coming and going. But some were always there. I have to give a big thanks to the permanent staff; Willem, Ina, Willy, Ed, Wya, Joop, Gesinda, Corien, Babs, Jelly, Hans, Minnie, Rene D, Betsy, Chris, Prashant, Jelmer, Henny, Patrick and Romana for all the smiles around the department. And a special thanks to Willem for all the chocolates along this PhD!

It was also a pleasure to work with Prashant and Patrick. I specially thank Deepak for sharing the work that we did in one of the chapters in this thesis. Thank you for your enthusiasm and support!

I would like to thank all the colleagues with whom I worked in the department especially, Hilde, Anna, Adhi, Simon, Joana, Niar, Helen, Arina, Song, Bu, Bart, Brian, Vera, Rebecca, René R, Bart, Sara, Brandon, Akshay, Agnieszka, Deepak, Stefan, Steven, Mayeul, Felipe, Qihui, Philip, Ed and JP.

I am lucky enough to call some of these people as friends… when we are abroad our friends become a bit as our family. Thank you my dear Niar, Joana, Anna and Hilde! Thank you so, so much. I could write an acknowledgment section just for you. Without you surviving this PhD would be a (even) bigger challenge! Having you with me in and outside the department made me feel stronger. Thank you my girls!!

Also thank you my dear Helen, Brian, Feifei, Song, Bu, Arina. You made my life in the department easier. Having you around for lunch, dinner (inside or outside the department)

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173

A

172

“Human vocabulary is still not capable, and probably will never be, of knowing, recognizing, and communicating everything that can be humanly experienced and felt.” José Saramago

This PhD and this thesis are only possible mainly due to my supervisors, Theo van Kooten and Henk Busscher. Theo, you are the responsible for me to come to Groningen. With you I learned what is a calm and positive supervisor. You were always there for me. You always supported my decisions and you always gave me the freedom to “think”. I really appreciated that you had always your door open, to clarify my doubts or simply to “brainstorm”. Your positive feedback really boosted my self-esteem. I have learned so much with you and the way you teach. You were also responsible for my love for stainings and microscopy… maybe because we share another passion, photography! Thank you Theo, for your patience, your teachings, comprehension and for being always by my side.

Henk, thank you for making sure that this thesis would be finished. You took an important role in the end of this book. I really appreciate your efforts, even though you really didn’t have to…I had the opportunity to meet with you as a PhD representative and I always admired how fast you could solve problems. Thank you for the time you spent reading this thesis.

Another important person during my PhD was Roel Kuijer, my PCR teacher. Roel, like Theo you always gave me the possibility to share my ideas. And you were always very critical … I really appreciate that! Your critical comments always helped to significantly improve my articles. When I arrived at the BME department, I had a very “depressive” feeling about genetics and PCR in particular. I left with a very positive feeling about it. The reason for it was your patience to teach me, with my own mistakes. For that, but also for your kindness, I thank you.

I also thank the reading committee, prof. dr. Ruud A. Bank, prof. dr. Oliver Stachs and prof. dr. Klaas Nico Faber for the time spent reading this thesis.

This thesis was a truly collaborative work. The work was performed in close collaboration with medical doctors but also with companies. All parties played crucial roles for the success of the project. I have to thank dr. Steven Koopmans and Lisanne Nibourg for all the important inputs, done with an unique, medical perspective. And I also have to thank the people at Nano-FM; Menno de Jong, Edith Gelens, Erna Bulten and Annemarie Tuin. Without you, this thesis could never be finished. I deeply appreciate your efforts to provide me with the crucial biomaterials. You were also always ready to brainstorm, while taking a “warm” cup of coffee. Also, in thank Abbott for its confidence on the project.

Last but not least, I thank Kroon Vlees, for all the porcine materials used in this thesis but also for much more than that… For all the sympathy, and for all the chats while killing time in the slaughterhouse. I would like to thank in particular to Karina for all the kindness.

Before finishing this thesis I started to work at Wellinq. And I need to give a big thanks to everyone there, for receiving me so well at the company. Barry and Sander, thank you so much for allowing me to have the time I needed to finish this PhD thesis. But also for

173

much more than that, for trusting me and giving me the confidence to grow as a R&D. It has been an amazing experience and I am learning a lot from both of you. I also need to thank the fantastic people that work directly with me; Robert Splinter, Rein, Wouter, Wendy, Henk, Jan, Jannes, Azim, Robert, Rudi, Sjoukje, but also Fransisca, Annet and Herma, these amazing ladies. All the people on the workshop and, of course, the “great/huge” R&D team”; Erik, Gert-Jan, Jan Remke, Jeroen and Caroline. Thank you all, for “the good vibes”!!

But most importantly, Mart. You are one of the smartest person I ever met and I feel honored to be able to work with you. It is impossible to describe how much I have learned with you already. Thank you for being my teacher but also my friend. Thank you for your kindness, for your advices and for your time listen my ideas and “problems”. You are an example for me. Thank you for your support and for everything. I will miss you…

I started as a “fresh” portuguese PhD student in the BME department. I was fortunate to meet different people, from different countries and to be able to understand different cultures. This experience changed me forever! In the beginning, it was very difficult for me to “deal” with the dutch culture. But with time, I became more dutch than portuguese… And now I have to say that sometimes it is more difficult for me to understand the portuguese culture than the dutch one!

The department became my second house, mainly in the beginning of the PhD. I saw a lot of people coming and going. But some were always there. I have to give a big thanks to the permanent staff; Willem, Ina, Willy, Ed, Wya, Joop, Gesinda, Corien, Babs, Jelly, Hans, Minnie, Rene D, Betsy, Chris, Prashant, Jelmer, Henny, Patrick and Romana for all the smiles around the department. And a special thanks to Willem for all the chocolates along this PhD!

It was also a pleasure to work with Prashant and Patrick. I specially thank Deepak for sharing the work that we did in one of the chapters in this thesis. Thank you for your enthusiasm and support!

I would like to thank all the colleagues with whom I worked in the department especially, Hilde, Anna, Adhi, Simon, Joana, Niar, Helen, Arina, Song, Bu, Bart, Brian, Vera, Rebecca, René R, Bart, Sara, Brandon, Akshay, Agnieszka, Deepak, Stefan, Steven, Mayeul, Felipe, Qihui, Philip, Ed and JP.

I am lucky enough to call some of these people as friends… when we are abroad our friends become a bit as our family. Thank you my dear Niar, Joana, Anna and Hilde! Thank you so, so much. I could write an acknowledgment section just for you. Without you surviving this PhD would be a (even) bigger challenge! Having you with me in and outside the department made me feel stronger. Thank you my girls!!

Also thank you my dear Helen, Brian, Feifei, Song, Bu, Arina. You made my life in the department easier. Having you around for lunch, dinner (inside or outside the department) was always a pleasure! Thank you Brian and Feifei for this already long friendship.

173

much more than that, for trusting me and giving me the confidence to grow as a R&D. It has been an amazing experience and I am learning a lot from both of you. I also need to thank the fantastic people that work directly with me; Robert Splinter, Rein, Wouter, Wendy, Henk, Jan, Jannes, Azim, Robert, Rudi, Sjoukje, but also Fransisca, Annet and Herma, these amazing ladies. All the people on the workshop and, of course, the “great/huge” R&D team”; Erik, Gert-Jan, Jan Remke, Jeroen and Caroline. Thank you all, for “the good vibes”!!

But most importantly, Mart. You are one of the smartest person I ever met and I feel honored to be able to work with you. It is impossible to describe how much I have learned with you already. Thank you for being my teacher but also my friend. Thank you for your kindness, for your advices and for your time listen my ideas and “problems”. You are an example for me. Thank you for your support and for everything. I will miss you…

I started as a “fresh” portuguese PhD student in the BME department. I was fortunate to meet different people, from different countries and to be able to understand different cultures. This experience changed me forever! In the beginning, it was very difficult for me to “deal” with the dutch culture. But with time, I became more dutch than portuguese… And now I have to say that sometimes it is more difficult for me to understand the portuguese culture than the dutch one!

The department became my second house, mainly in the beginning of the PhD. I saw a lot of people coming and going. But some were always there. I have to give a big thanks to the permanent staff; Willem, Ina, Willy, Ed, Wya, Joop, Gesinda, Corien, Babs, Jelly, Hans, Minnie, Rene D, Betsy, Chris, Prashant, Jelmer, Henny, Patrick and Romana for all the smiles around the department. And a special thanks to Willem for all the chocolates along this PhD!

It was also a pleasure to work with Prashant and Patrick. I specially thank Deepak for sharing the work that we did in one of the chapters in this thesis. Thank you for your enthusiasm and support!

I would like to thank all the colleagues with whom I worked in the department especially, Hilde, Anna, Adhi, Simon, Joana, Niar, Helen, Arina, Song, Bu, Bart, Brian, Vera, Rebecca, René R, Bart, Sara, Brandon, Akshay, Agnieszka, Deepak, Stefan, Steven, Mayeul, Felipe, Qihui, Philip, Ed and JP.

I am lucky enough to call some of these people as friends… when we are abroad our friends become a bit as our family. Thank you my dear Niar, Joana, Anna and Hilde! Thank you so, so much. I could write an acknowledgment section just for you. Without you surviving this PhD would be a (even) bigger challenge! Having you with me in and outside the department made me feel stronger. Thank you my girls!!

Also thank you my dear Helen, Brian, Feifei, Song, Bu, Arina. You made my life in the department easier. Having you around for lunch, dinner (inside or outside the department) was always a pleasure! Thank you Brian and Feifei for this already long friendship.

173

much more than that, for trusting me and giving me the confidence to grow as a R&D. It has been an amazing experience and I am learning a lot from both of you. I also need to thank the fantastic people that work directly with me; Robert Splinter, Rein, Wouter, Wendy, Henk, Jan, Jannes, Azim, Robert, Rudi, Sjoukje, but also Fransisca, Annet and Herma, these amazing ladies. All the people on the workshop and, of course, the “great/huge” R&D team”; Erik, Gert-Jan, Jan Remke, Jeroen and Caroline. Thank you all, for “the good vibes”!!

But most importantly, Mart. You are one of the smartest person I ever met and I feel honored to be able to work with you. It is impossible to describe how much I have learned with you already. Thank you for being my teacher but also my friend. Thank you for your kindness, for your advices and for your time listen my ideas and “problems”. You are an example for me. Thank you for your support and for everything. I will miss you…

I started as a “fresh” portuguese PhD student in the BME department. I was fortunate to meet different people, from different countries and to be able to understand different cultures. This experience changed me forever! In the beginning, it was very difficult for me to “deal” with the dutch culture. But with time, I became more dutch than portuguese… And now I have to say that sometimes it is more difficult for me to understand the portuguese culture than the dutch one!

The department became my second house, mainly in the beginning of the PhD. I saw a lot of people coming and going. But some were always there. I have to give a big thanks to the permanent staff; Willem, Ina, Willy, Ed, Wya, Joop, Gesinda, Corien, Babs, Jelly, Hans, Minnie, Rene D, Betsy, Chris, Prashant, Jelmer, Henny, Patrick and Romana for all the smiles around the department. And a special thanks to Willem for all the chocolates along this PhD!

It was also a pleasure to work with Prashant and Patrick. I specially thank Deepak for sharing the work that we did in one of the chapters in this thesis. Thank you for your enthusiasm and support!

I would like to thank all the colleagues with whom I worked in the department especially, Hilde, Anna, Adhi, Simon, Joana, Niar, Helen, Arina, Song, Bu, Bart, Brian, Vera, Rebecca, René R, Bart, Sara, Brandon, Akshay, Agnieszka, Deepak, Stefan, Steven, Mayeul, Felipe, Qihui, Philip, Ed and JP.

I am lucky enough to call some of these people as friends… when we are abroad our friends become a bit as our family. Thank you my dear Niar, Joana, Anna and Hilde! Thank you so, so much. I could write an acknowledgment section just for you. Without you surviving this PhD would be a (even) bigger challenge! Having you with me in and outside the department made me feel stronger. Thank you my girls!!

Also thank you my dear Helen, Brian, Feifei, Song, Bu, Arina. You made my life in the department easier. Having you around for lunch, dinner (inside or outside the department) was always a pleasure! Thank you Brian and Feifei for this already long friendship.

173

has been an amazing experience and I am learning a lot from both of you. I also need to thank the fantastic people that work directly with me; Robert Splinter, Rein, Wouter, Wendy, Henk, Jan, Jannes, Azim, Robert, Rudi, Sjoukje, but also Fransisca, Annet and Herma, these amazing ladies. All the people on the workshop and, of course, the “great/huge” R&D team”; Erik, Gert-Jan, Jan Remke, Jeroen and Caroline. Thank you all, for “the good vibes”!!

But most importantly, Mart. You are one of the smartest person I ever met and I feel honored to be able to work with you. It is impossible to describe how much I have learned with you already. Thank you for being my teacher but also my friend. Thank you for your kindness, for your advices and for your time listen my ideas and “problems”. You are an example for me. Thank you for your support and for everything. I will miss you…

I started as a “fresh” portuguese PhD student in the BME department. I was fortunate to meet different people, from different countries and to be able to understand different cultures. This experience changed me forever! In the beginning, it was very difficult for me to “deal” with the dutch culture. But with time, I became more dutch than portuguese… And now I have to say that sometimes it is more difficult for me to understand the portuguese culture than the dutch one!

The department became my second house, mainly in the beginning of the PhD. I saw a lot of people coming and going. But some were always there. I have to give a big thanks to the permanent staff; Willem, Ina, Willy, Ed, Wya, Joop, Gesinda, Corien, Babs, Jelly, Hans, Minnie, Rene D, Betsy, Chris, Prashant, Jelmer, Henny, Patrick and Romana for all the smiles around the department. And a special thanks to Willem for all the chocolates along this PhD!

It was also a pleasure to work with Prashant and Patrick. I specially thank Deepak for sharing the work that we did in one of the chapters in this thesis. Thank you for your enthusiasm and support!

I would like to thank all the colleagues with whom I worked in the department especially, Hilde, Anna, Adhi, Simon, Joana, Niar, Helen, Arina, Song, Bu, Bart, Brian, Vera, Rebecca, René R, Bart, Sara, Brandon, Akshay, Agnieszka, Deepak, Stefan, Steven, Mayeul, Felipe, Qihui, Philip, Ed and JP.

I am lucky enough to call some of these people as friends… when we are abroad our friends become a bit as our family. Thank you my dear Niar, Joana, Anna and Hilde! Thank you so, so much. I could write an acknowledgment section just for you. Without you surviving this PhD would be a (even) bigger challenge! Having you with me in and outside the department made me feel stronger. Thank you my girls!!

Also thank you my dear Helen, Brian, Feifei, Song, Bu, Arina. You made my life in the department easier. Having you around for lunch, dinner (inside or outside the department) was always a pleasure! Thank you Brian and Feifei for this already long friendship.

173

much more than that, for trusting me and giving me the confidence to grow as a R&D. It has been an amazing experience and I am learning a lot from both of you. I also need to thank the fantastic people that work directly with me; Robert Splinter, Rein, Wouter, Wendy, Henk, Jan, Jannes, Azim, Robert, Rudi, Sjoukje, but also Fransisca, Annet and Herma, these amazing ladies. All the people on the workshop and, of course, the “great/huge” R&D team”; Erik, Gert-Jan, Jan Remke, Jeroen and Caroline. Thank you all, for “the good vibes”!!

But most importantly, Mart. You are one of the smartest person I ever met and I feel honored to be able to work with you. It is impossible to describe how much I have learned with you already. Thank you for being my teacher but also my friend. Thank you for your kindness, for your advices and for your time listen my ideas and “problems”. You are an example for me. Thank you for your support and for everything. I will miss you…

I started as a “fresh” portuguese PhD student in the BME department. I was fortunate to meet different people, from different countries and to be able to understand different cultures. This experience changed me forever! In the beginning, it was very difficult for me to “deal” with the dutch culture. But with time, I became more dutch than portuguese… And now I have to say that sometimes it is more difficult for me to understand the portuguese culture than the dutch one!

The department became my second house, mainly in the beginning of the PhD. I saw a lot of people coming and going. But some were always there. I have to give a big thanks to the permanent staff; Willem, Ina, Willy, Ed, Wya, Joop, Gesinda, Corien, Babs, Jelly, Hans, Minnie, Rene D, Betsy, Chris, Prashant, Jelmer, Henny, Patrick and Romana for all the smiles around the department. And a special thanks to Willem for all the chocolates along this PhD!

It was also a pleasure to work with Prashant and Patrick. I specially thank Deepak for sharing the work that we did in one of the chapters in this thesis. Thank you for your enthusiasm and support!

I would like to thank all the colleagues with whom I worked in the department especially, Hilde, Anna, Adhi, Simon, Joana, Niar, Helen, Arina, Song, Bu, Bart, Brian, Vera, Rebecca, René R, Bart, Sara, Brandon, Akshay, Agnieszka, Deepak, Stefan, Steven, Mayeul, Felipe, Qihui, Philip, Ed and JP.

I am lucky enough to call some of these people as friends… when we are abroad our friends become a bit as our family. Thank you my dear Niar, Joana, Anna and Hilde! Thank you so, so much. I could write an acknowledgment section just for you. Without you surviving this PhD would be a (even) bigger challenge! Having you with me in and outside the department made me feel stronger. Thank you my girls!!

Also thank you my dear Helen, Brian, Feifei, Song, Bu, Arina. You made my life in the department easier. Having you around for lunch, dinner (inside or outside the department) was always a pleasure! Thank you Brian and Feifei for this already long friendship.

173

much more than that, for trusting me and giving me the confidence to grow as a R&D. It has been an amazing experience and I am learning a lot from both of you. I also need to thank the fantastic people that work directly with me; Robert Splinter, Rein, Wouter, Wendy, Henk, Jan, Jannes, Azim, Robert, Rudi, Sjoukje, but also Fransisca, Annet and Herma, these amazing ladies. All the people on the workshop and, of course, the “great/huge” R&D team”; Erik, Gert-Jan, Jan Remke, Jeroen and Caroline. Thank you all, for “the good vibes”!!

But most importantly, Mart. You are one of the smartest person I ever met and I feel honored to be able to work with you. It is impossible to describe how much I have learned with you already. Thank you for being my teacher but also my friend. Thank you for your kindness, for your advices and for your time listen my ideas and “problems”. You are an example for me. Thank you for your support and for everything. I will miss you…

I started as a “fresh” portuguese PhD student in the BME department. I was fortunate to meet different people, from different countries and to be able to understand different cultures. This experience changed me forever! In the beginning, it was very difficult for me to “deal” with the dutch culture. But with time, I became more dutch than portuguese… And now I have to say that sometimes it is more difficult for me to understand the portuguese culture than the dutch one!

The department became my second house, mainly in the beginning of the PhD. I saw a lot of people coming and going. But some were always there. I have to give a big thanks to the permanent staff; Willem, Ina, Willy, Ed, Wya, Joop, Gesinda, Corien, Babs, Jelly, Hans, Minnie, Rene D, Betsy, Chris, Prashant, Jelmer, Henny, Patrick and Romana for all the smiles around the department. And a special thanks to Willem for all the chocolates along this PhD!

It was also a pleasure to work with Prashant and Patrick. I specially thank Deepak for sharing the work that we did in one of the chapters in this thesis. Thank you for your enthusiasm and support!

I would like to thank all the colleagues with whom I worked in the department especially, Hilde, Anna, Adhi, Simon, Joana, Niar, Helen, Arina, Song, Bu, Bart, Brian, Vera, Rebecca, René R, Bart, Sara, Brandon, Akshay, Agnieszka, Deepak, Stefan, Steven, Mayeul, Felipe, Qihui, Philip, Ed and JP.

I am lucky enough to call some of these people as friends… when we are abroad our friends become a bit as our family. Thank you my dear Niar, Joana, Anna and Hilde! Thank you so, so much. I could write an acknowledgment section just for you. Without you surviving this PhD would be a (even) bigger challenge! Having you with me in and outside the department made me feel stronger. Thank you my girls!!

Also thank you my dear Helen, Brian, Feifei, Song, Bu, Arina. You made my life in the department easier. Having you around for lunch, dinner (inside or outside the department) was always a pleasure! Thank you Brian and Feifei for this already long friendship.

(5)

Acknowledgements

Along of these years I met other friends that also make me feel at home in Groningen. Olga, Elena, Isis, Genaro, Alexandro, Valentina, Annabelle, Soraia, Faustine, Magdalena and Mary, thank you for all the good moments and nice chats!

Julieth, you have a special place in my life as well as in this acknowledgments… you are my best friend! I think I could never express the feeling of gratitude that I have for you. Thank you so much for all the support, comprehension and for the friendship. Thank you for always understanding me! Thank you for everything…

I also have to thank the friends that I “left” in Portugal. Although good friends are never far away from our hearts... Thank you Zé and Catarina, for all the good times that we spent together, and for all the support, especially in the beginning of this PhD. Thank you Maria Victoria! Thank you so much for your help, every time that I needed it. Thank you guys for always make time for me, when I need but also when I don’t really need it!

Minha querida Sandra, a “minha Sandra”... acho que isto já diz tudo! Friendship “flies over time” e nós somos a prova disso! As palavras nunca serão suficiente para te agradecer. Nunca te conseguirei agradecer o tempo que tens para mim, nunca te conseguirei agradecer a confiança, a amizade... Sou muito sortuda em ter-te na minha vida! Obrigada... obrigada, obrigada!

To all my family, para a minha família, a quem só tenho de agradecer todo o amor desde que me lembro de ser gente. À minha família que sempre me apoiou e me dá forças para estar aqui, obrigada, muito obrigada! Tio João e tia Madalena, os melhores padrinhos que os meus pais me podiam ter escolhido. Obrigada por me fazerem sentir sempre (e desde de sempre) tão amada. Pedro e Belinha, primos e protectores da minha infância, obrigada por todo o vosso apoio!! E obrigada por trazerem gente tão fixe para a família, Fatinha e Pedro Filipe. E especial obrigada ao Pedro e à Fatinha por me darem dois priminhos tão fofinhos, João Pedro e Martim. Espero que cresçam para poderem passar mais tempo comigo aqui na Holanda...

Também tive a sorte de ter entrado para a minha vida o melhor cunhado do mundo! E estas palavras não são exageradas! Pedro (Miguel), obrigada do fundo do coração por seres um verdadeiro amigo e por cuidares da minha irmã. Se ela está bem eu também estou bem. E obrigada por todo o apoio e carinho! Contigo trouxeste pessoas fantásticas! D. Zi, sr. Camilo, obrigada por todo o carinho… muito obrigada! E obrigada a todo o resto da família em geral por todos os almoços e carinho!

E, como sou mesmo uma sortuda, entraram também na minha vida uma nova família! D. Teresa, sr. Alberto, Carolina, Rui e bebé (), obrigada por todo o apoio e por torcerem sempre por mim! Obrigada por me acolherem sempre tão bem e me fazerem sentir parte da “vossa” família também. Muito obrigada.

Ao meu querido afilhado, Hugo. Huguinho, minha alma doce, terás sempre um lugar especial no meu coração e vou estar sempre aqui para te ajudar. Obrigada por todo o

À minha afilhada e sobrinha, a minha pestinha, minha querida Sofia. Tu fizeste-me descobrir um amor novo e custa-me muito estar longe de ti… se calhar vais gostar de ciência como eu, e se calhar um dia vais ler esta tese, eu gostava muito! Mas o que quero é que sejas muito feliz! Não tenhas pressa de crescer minha princesinha.

A minha irmã é provavelmente a razão pela qual eu segui ciência. Sílvia, lembro-me bem de pequenina ir contigo ao laboratório e me fascinar com todos os frascos e cores! Tu foste o meu exemplo! E podia tentar descrever o quanto és importante para mim mas nunca o iria conseguir… Sempre foste a minha protectora e sempre me apoias-te em tudo! Se calhar sem ti tinha ido embora daqui e esta tese não existia… obrigada por não teres deixado isso acontecer! Obrigada por seres o meu pilar. E obrigada por (ainda) cuidares tão bem de mim!

Mãe, pai! Esta tese também é vossa… Graças a vocês e à educação que sempre me deram é que estou aqui… sempre me incentivaram a ir mais longe e a lutar. Obrigada por todos os sacrifícios que fizeram por mim, por todo o apoio e por todo o amor. Obrigada por serem o meu porto de abrigo, obrigada por ter sempre o meu lugar em casa. Nunca vós irei agradecer o suficiente… obrigada, obrigada!

Six years ago I met, in a train trip, a person. He was a bit frightful, but friendly and distracted, very distracted. He had with him all problems of the world, but he tried to show me that he could still carry on. Now, when I think of him, my heart is flooded with happiness. And I can try to describe my feelings for him but then I would write an infinite sentence. It's better to tell him every day that I love him.Carlos… tu és a outra parte de mim. Tu és o meu complemento. Tu ensinas-me todos os dias! Admiro-te! Admiro a tua perseverança, a tua força… Obrigada por nunca teres desistido de nós. Obrigada por compreenderes todas as horas que não passamos juntos para poder acabar esta tese… Não, não foi amor à primeira vista…foi bem melhor que isso! É amor para sempre.

(6)

175

A

174

Along of these years I met other friends that also make me feel at home in Groningen. Olga, Elena, Isis, Genaro, Alexandro, Valentina, Annabelle, Soraia, Faustine, Magdalena and Mary, thank you for all the good moments and nice chats!

Julieth, you have a special place in my life as well as in this acknowledgments… you are my best friend! I think I could never express the feeling of gratitude that I have for you. Thank you so much for all the support, comprehension and for the friendship. Thank you for always understanding me! Thank you for everything…

I also have to thank the friends that I “left” in Portugal. Although good friends are never far away from our hearts... Thank you Zé and Catarina, for all the good times that we spent together, and for all the support, especially in the beginning of this PhD. Thank you Maria Victoria! Thank you so much for your help, every time that I needed it. Thank you guys for always make time for me, when I need but also when I don’t really need it!

Minha querida Sandra, a “minha Sandra”... acho que isto já diz tudo! Friendship “flies over time” e nós somos a prova disso! As palavras nunca serão suficiente para te agradecer. Nunca te conseguirei agradecer o tempo que tens para mim, nunca te conseguirei agradecer a confiança, a amizade... Sou muito sortuda em ter-te na minha vida! Obrigada... obrigada, obrigada!

To all my family, para a minha família, a quem só tenho de agradecer todo o amor desde que me lembro de ser gente. À minha família que sempre me apoiou e me dá forças para estar aqui, obrigada, muito obrigada! Tio João e tia Madalena, os melhores padrinhos que os meus pais me podiam ter escolhido. Obrigada por me fazerem sentir sempre (e desde de sempre) tão amada. Pedro e Belinha, primos e protectores da minha infância, obrigada por todo o vosso apoio!! E obrigada por trazerem gente tão fixe para a família, Fatinha e Pedro Filipe. E especial obrigada ao Pedro e à Fatinha por me darem dois priminhos tão fofinhos, João Pedro e Martim. Espero que cresçam para poderem passar mais tempo comigo aqui na Holanda...

Também tive a sorte de ter entrado para a minha vida o melhor cunhado do mundo! E estas palavras não são exageradas! Pedro (Miguel), obrigada do fundo do coração por seres um verdadeiro amigo e por cuidares da minha irmã. Se ela está bem eu também estou bem. E obrigada por todo o apoio e carinho! Contigo trouxeste pessoas fantásticas! D. Zi, sr. Camilo, obrigada por todo o carinho… muito obrigada! E obrigada a todo o resto da família em geral por todos os almoços e carinho!

E, como sou mesmo uma sortuda, entraram também na minha vida uma nova família! D. Teresa, sr. Alberto, Carolina, Rui e bebé (), obrigada por todo o apoio e por torcerem sempre por mim! Obrigada por me acolherem sempre tão bem e me fazerem sentir parte da “vossa” família também. Muito obrigada.

Ao meu querido afilhado, Hugo. Huguinho, minha alma doce, terás sempre um lugar especial no meu coração e vou estar sempre aqui para te ajudar. Obrigada por todo o carinho e por todo o orgulho que tens em mim. Este doutoramento trouxe-me ainda menos tempo para te ver… espero que isso mude!

175

À minha afilhada e sobrinha, a minha pestinha, minha querida Sofia. Tu fizeste-me descobrir um amor novo e custa-me muito estar longe de ti… se calhar vais gostar de ciência como eu, e se calhar um dia vais ler esta tese, eu gostava muito! Mas o que quero é que sejas muito feliz! Não tenhas pressa de crescer minha princesinha.

A minha irmã é provavelmente a razão pela qual eu segui ciência. Sílvia, lembro-me bem de pequenina ir contigo ao laboratório e me fascinar com todos os frascos e cores! Tu foste o meu exemplo! E podia tentar descrever o quanto és importante para mim mas nunca o iria conseguir… Sempre foste a minha protectora e sempre me apoias-te em tudo! Se calhar sem ti tinha ido embora daqui e esta tese não existia… obrigada por não teres deixado isso acontecer! Obrigada por seres o meu pilar. E obrigada por (ainda) cuidares tão bem de mim!

Mãe, pai! Esta tese também é vossa… Graças a vocês e à educação que sempre me deram é que estou aqui… sempre me incentivaram a ir mais longe e a lutar. Obrigada por todos os sacrifícios que fizeram por mim, por todo o apoio e por todo o amor. Obrigada por serem o meu porto de abrigo, obrigada por ter sempre o meu lugar em casa. Nunca vós irei agradecer o suficiente… obrigada, obrigada!

Six years ago I met, in a train trip, a person. He was a bit frightful, but friendly and distracted, very distracted. He had with him all problems of the world, but he tried to show me that he could still carry on. Now, when I think of him, my heart is flooded with happiness. And I can try to describe my feelings for him but then I would write an infinite sentence. It's better to tell him every day that I love him.Carlos… tu és a outra parte de mim. Tu és o meu complemento. Tu ensinas-me todos os dias! Admiro-te! Admiro a tua perseverança, a tua força… Obrigada por nunca teres desistido de nós. Obrigada por compreenderes todas as horas que não passamos juntos para poder acabar esta tese… Não, não foi amor à primeira vista…foi bem melhor que isso! É amor para sempre.

(7)

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