PROBING CELLULAR MECHANO-SENSITIVITY USING BIOMEMBRANE-MIMICKING CELL SUBSTRATES OF ADJUSTABLE STIFFNESS

It is increasingly recognized that mechanical properties of substrates play a pivotal role in the regulation of cellular fate and function. However, the underlying mechanisms of cellular mechanosensing still remain a topic of open debate. Traditionally, advancements in this field have been made using polymeric substrates of adjustable stiffness with immobilized linkers. While such substrates are well suited to examine cell adhesion and migration in an extracellular matrix environment, they are limited in their ability to replicate the rich dynamics found at cell-cell interfaces. To address this challenge, we recently introduced a linker-functionalized polymer-tethered multi-bilayer stack, in which substrate stiffness can be altered by the degree of bilayer stacking, thus allowing the analysis of cellular mechanosensitivity. Here, we apply this novel biomembrane-mimicking cell substrate design to explore the mechanosensitivity of C2C12 myoblasts in the presence of cell-cell-mimicking N-cadherin linkers. Experiments are presented, which demonstrate a relationship between the degree of bilayer stacking and mechanoresponse of plated cells, such as morphology, cytoskeletal organization, cellular traction forces, and migration speed. Furthermore, we illustrate the dynamic assembly of bilayer-bound N-cadherin linkers underneath cellular adherens junctions. In addition, properties of individual and clustered N-cadherins are examined in the polymer-tethered bilayer system in the absence of plated cells.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Year

2015

Author dc:creator

• Lin, Yu-Hung

Contributors dc:contributor

• Christoph A Naumann
• Eric Long
• David Thompson
• Chittaranjan Das

• Artificial Substrates
• Biomembrane-mimicking
• Cadherin
• Cellular Mechanoresponse
• Lipid Bilayer
• Polymer-tethered

Repository record dc:identifier

https://docs.lib.purdue.edu/open_access_dissertations/1442

OAI identifier oai:identifier

oai:docs.lib.purdue.edu:open_access_dissertations-2658