Abstract
Mechanics is an important component in the regulation of cell shape, proliferation, migration and differentiation during normal homeostasis and disease states. Biomaterials that match the elastic modulus of soft tissues have been effective for studying this cell mechanobiology, but improvements are needed in order to investigate a wider range of physicochemical properties in a controlled manner. We hypothesized that polydimethylsiloxane (PDMS) blends could be used as the basis of a tunable system where the elastic modulus could be adjusted to match most types of soft tissue. To test this we formulated blends of two commercially available PDMS types, Sylgard 527 and Sylgard 184, which enabled us to fabricate substrates with an elastic modulus anywhere from 5 kPa up to 1.72 MPa. This is a three order-of-magnitude range of tunability, exceeding what is possible with other hydrogel and PDMS systems. Uniquely, the elastic modulus can be controlled independently of other materials properties including surface roughness, surface energy and the ability to functionalize the surface by protein adsorption and microcontact printing. For biological validation, PC12 (neuronal inducible-pheochromocytoma cell line) and C2C12 (muscle cell line) were used to demonstrate that these PDMS formulations support cell attachment and growth and that these substrates can be used to probe the mechanosensitivity of various cellular processes including neurite extension and muscle differentiation.
Highlights
Over the past decade it has become evident that the mechanical environment has a profound effect on cell survival, proliferation, adhesion, differentiation and metabolism [1,2,3,4,5,6,7,8]
In 2006 Engler et al demonstrated that mesenchymal stem cell specification on collagen coated PA gels was directed towards neurons, muscle and bone on substrates that matched the elastic modulus of these tissues [1]
Recent work in cancer biology has revealed that the extracellular matrix (ECM) in tumors is characterized by increased stiffness and that ECM remodeling can lead to invasion and metastasis [9,10]
Summary
Over the past decade it has become evident that the mechanical environment has a profound effect on cell survival, proliferation, adhesion, differentiation and metabolism [1,2,3,4,5,6,7,8]. Stem cells are sensitive to ECM and substrate mechanics [8], where control of stiffness can drive differentiation into specific lineages [1,7] or maintain stem cells in a pluripotent state [6]. The commonalities between these studies are experimental tools that control the mechanical environment of cells by modulating the stresses and/or strains cells sense and respond to. Understanding this underlying mechanobiology is important in order to develop improved platforms for in vitro cell analysis, tissue engineering scaffolds and regenerative medicine strategies
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