Defining the role of matrix compliance and proteolysis in three-dimensional cell spreading and remodeling

Biophysical Journal
Daniel DikovskyD Seliktar

Abstract

Recent studies have identified extracellular matrix (ECM) compliance as an influential factor in determining the fate of anchorage-dependent cells. We explore a method of examining the influence of ECM compliance on cell morphology and remodeling in three-dimensional culture. For this purpose, a biological ECM analog material was developed to pseudo-independently alter its biochemical and physical properties. A set of 18 material variants were prepared with shear modulus ranging from 10 to 700 Pa. Smooth muscle cells were encapsulated in these materials and time-lapse video microscopy was used to show a relationship between matrix modulus, proteolytic biodegradation, cell spreading, and cell compaction of the matrix. The proteolytic susceptibility of the matrix, the degree of matrix compaction, and the cell morphology were quantified for each of the material variants to correlate with the modulus data. The initial cell spreading into the hydrogel matrix was dependent on the proteolytic susceptibility of the materials, whereas the extent of cell compaction proved to be more correlated to the modulus of the material. Inhibition of matrix metalloproteinases profoundly affected initial cell spreading and remodeling even in the most...Continue Reading

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