The stiffness of collagen fibrils influences vascular smooth muscle cell phenotype

¹ National Institute of Standards and Technology
² SAIC

^* To whom correspondence should be addressed. E-mail: anne.plant{at}nist.gov.

Submitted on May 17, 2006
Revised on July 14, 2006
Accepted on 14 November 2006

	Abstract

Cells receive signals from the extracellular matrix through receptor-dependent interactions, but they are also influenced by the mechanical properties of the matrix. While bulk mechanical properties of substrates have been shown to effect cell behavior, we show here that nanoscale mechanical properties of collagen fibrils also play a significant role in determining cell phenotype. Type I collagen fibrils assembled into thin films provide excellent viewing of cells interacting with individual fibrils. Cells can be observed to extensively manipulate the fibrils, and this behavior seems to result in an incompletely spread stellate morphology and a nonproliferative phenotype that is typical of these cells in collagen gels. We show here that thin films of collagen fibrils can be dehydrated, and when seeded on these dehydrated fibrils, smooth muscle cells spread and proliferate extensively. The dehydrated collagen fibrils appear to be similar to the fully hydrated collagen fibrils in topology and in presentation of 1 integrin ligation sites, but they are mechanically stiffer. This decrease in compliance of dehydrated fibrils is seen by a failure of cell movement of dehydrated fibrils compared to their ability to rearrange fully hydrated fibrils, and from direct measurements by nanoindentation and quantitative atomic force measurements. We suggest that increase in the nanoscale rigidity of collagen fibrils can cause these cells to assume a proliferative phenotype.

Key Words: alkanethiol self-assembled monolayer, collagen Type 1, extracellular matrix, mechanical properties, optical microscopy, supramolecular structure

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