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 properties of substrates have been shown to effect cell behavior, we show here that nanoscale 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 dehydrated fibrils, smooth muscle cells spread and proliferate extensively. The dehydrated collagen fibrils do not differ from the fully hydrated collagen fibrils in topology or in presentation of ?1 integrin ligation sites, but they are mechanically stiffer. This decrease in compliance of dehydrated fibrils is directly determined by nanoindentation and quantitative atomic force measurements. We hypothesize that it the nanoscale rigidity of collagen fibrils that causes cells to assume a proliferative phenotype.
Citation: Biophysical Journal
Pub Type: Journals
alkanethiol self-assembled monolayers, biopolymer, collagen I, extracellular matrix, mechanical stiffness, optical microscopy, phenotype, supramolecular structure, vascular smooth muscle cells