A Composite Microstructural Substrate with Stiffness Gradient for the Study of Cell Migration
Date Issued
2012
Date
2012
Author(s)
Shen, Shou-Chien
Abstract
Cell interaction with their physical environment has been shown to play an important role in physiological processes, including morphogenesis, immune response, wound healing, and tumor metastasis. Recent studies have demonstrated that preferential migration of cells toward mechanically stiff regions; a process known as durotaxis. However, much of this phenomenon is still not fully understood. In this study, we developed a novel system of a continuous stiffness gradient with a collagen hydrogel-based composite microstructural substrate. Our results indicated that induction of durotaxis depends on the magnitude of the elasticity jump. In addition, our results provide a quantitative confirmation that increases in cell density reduce cell durotaxis, which can be observed only at low cell density, where there is less cell-cell interaction. Pharmacologic inhibition studies suggested that cell migration directed by substrate mechanical stiffness was regulated by a Rho- and myosin-dependent cell contractility mechanism. This novel platform allows for better understanding of the cellular response to substrate stiffness gradients and the underlying molecular mechanisms.
Subjects
Cell migration
stiffness gradient
cytoskeleton
cell mechanics
atomic force microscopy
Type
thesis
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