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Multiparametric Measurement and Analysis of Cell Behavior on Extracellular Matrices
Summary
Cell responses to their culture environment always involve more than one component. An understanding of the relation between the physical and chemical features of the extracellular matrix (ECM) and the related cell responses, allows the rational design and development of cell-interacting biomaterials, for biomedical applications. Using type I collagen matrices as a model ECM, we are examining what factors, or properties of the ECM, elicit which specific cellular responses.
Description
The rational design of biomaterials which can elicit desired cellular responses is an important requirement for tissue engineering. Understanding the role of different cues that extracellular matrices provide cells is an important component of achieving this objective. Type 1 collagen is a ubiquitous extracellular matrix in the body, and is a major component of the medial layer of the large vessels, populated by vascular smooth muscle cells. Cells adhere to type I collagen through both integrin and non-integrin receptors, and are known to respond to both the mechanical stiffness, and supramolecular organization, of collagen. Using an engineered extracellular matrix comprised of a thin film of collagen fibrils, or a monolayer of collagen, we examined how the molecular presentation of type 1 collagen influence signaling in cultured vSMC. Our findings thus far suggest that different properties of collagen, specifically its molecular presentation, elicit distinct cell responses, and this must potentially be a consideration in biomaterial design involving type I collagen.
Major Accomplishments
- Identified three, orthogonal characteristics of type I collagen matrices that evoke apparently distinct cellular responses
Bhadriraju K, Chung KH, Spurlin TA, Haynes RJ, Elliott JT et al. (2009) The relative roles of collagen adhesive receptor DDR2 activation and matrix stiffness on the downregulation of focal adhesion kinase in vascular smooth muscle cells. Biomaterials 30: 6687-6694. doi:10.1016/j.biomaterials.2009.08.036.