Understanding the chemical complexity of the extracellular matrix (ECM) and how chemical, biological, and physical cues bring changes to the behavior of cells has remained a grand challenge. Addressing these questions requires not only achieving systematic control over the interactions between cells and the ECM but also utilizing suitable analytical techniques that can offer a quantitative readout of intracellular biochemical changes. Here, polymer pen lithography (PPL) and self-assembled monolayer laser desorption/ionization (SAMDI) mass spectrometry are uniquely positioned to offer researchers nanoscale surface fabrication and analytical tools that have significant advantages for creating cell-based assays on molecularly encoded surfaces, respectively. Chapter 1 gives an overview of how researchers are recapitulating the complexity of the ECM microenvironment, and describes how PPL and SAMDI-MS, as surface fabrication and characterization techniques, can be used to answer fundamental questions about cell-substrate interactions and develop powerful cell-based assays. Chapter 2 describes a methodology for generating nanopatterned substrates for combinatorial studies involving cell behavior. Building upon this work, in Chapter 3 we utilize PPL to generate nanopatterns that can template the behavior of the cytoskeleton and program the fate of mesenchymal stem cells. These results show that PPL offers an unparalleled advantage over current printing approaches because it allows rapid prototyping of user-defined designs. More importantly, this work shows that the cytoskeleton can be manipulated in a user-defined fashion to build organized sub-cellular structures and induce programmed cell differentiation. Chapters 4 and 5 combine nanolithography with mass spectrometry to enable high-throughput cell-based assays with molecular readouts. Finally in Chapter 6, we summarize these concepts and demonstrate how the work presented in this thesis provides fundamental insight to into the role that ECM cues play in programming cell behavior as well as how cell-based assays that can capture biochemical events within cells can be developed. Overall, this work provides a comprehensive view geared towards defining surface chemistry for

Last modified

• 04/29/2019

Creator

• Maria de Lourdes Cabezas

DOI

• https://doi.org/10.21985/N20499

Subject

• 2018-01-01

Keyword

• mass spectrometry
• focal adhesions
• mesenchymal stem cell
• nanotechnology
• screening
• extracellular matrix

Resource type

• Dissertation

Rights statement

• In Copyright