Tissue cells exhibit varying responses according to the stiffness of their extracellular matrix (ECM). The mechanism of this stiffness sensing is not fully understood; however, it is known that cells probe stiffness by applying intracellular force to the ECM via integrin-mediated focal adhesions. The bonds between integrins and ECM have been described as “catch bonds”, and it is unclear how ECM viscoelasticity affects these bonds. We have observed the effects of ECM stiffness on the binding strength of integrins to ECM ligands by measuring the dissociation force of individual integrin-ligand bonds of 3T3 fibroblasts on collagen-coated polyacrylamide gels using atomic force microscopy. Results show that integrins exhibit higher rates of activation on stiff substrates. Furthermore, increased matrix stiffness results in the occurrence of larger, multi-bond dissociation events, which suggests that substrate stiffness may affect the cellular response by promoting integrin clustering as well as by modulating the maximum possible force between individual integrins and the ECM.

Creator

• Thomas, Gawain M.

Contributors

• Wen, Qi
• Iannacchione, Germano S.
• Burnham, Nancy A.

Degree

• MS

Unit

• Physics

Publisher

• Worcester Polytechnic Institute

Language

• English

Identifier

• etd-011917-141439

Keyword

• Cell adhesion
• cell signaling
• Atomic Force Microscopy

Advisor

• Wen, Qi

Committee

• Burnham, Nancy A.
• Iannacchione, Germano S.

Defense date

• 2016-12-14

Year

• 2017

Date created

• 2017-01-19

Resource type

• Thesis

Rights statement

• In Copyright