Tissue biomechanics regulate a wide range of cellular functions, but the influences on epidermal homeostasis and repair remain unclear. Here, we examined the role of extracellular matrix stiffness on human keratinocyte behavior using elastomeric substrates with defined mechanical properties. Increased matrix stiffness beyond normal physiologic levels promoted keratinocyte proliferation but did not alter the ability to self-renew or terminally differentiate. Activation of epidermal growth factor (EGF) signaling mediated the proliferative response to matrix stiffness and depended on focal adhesion assembly and cytoskeletal tension. Comparison of normal skin with keloid scar tissue further revealed an up-regulation of EGF signaling within the epidermis of stiffened scar tissue. We conclude that matrix stiffness regulates keratinocyte proliferation independently of changes in cell fate and is mediated by EGF signaling. These findings provide mechanistic insights into how keratinocytes sense and respond to their mechanical environment and suggest that matrix biomechanics may play a role in the pathogenesis keloid scar formation.
|Journal||Journal of Cell Science|
|Early online date||18 Apr 2018|
|Publication status||Early online - 18 Apr 2018|
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Data availability statement for 'Tissue stiffening promotes keratinocyte proliferation via activation of epidermal growth factor signaling'.
Kenny, F. (Creator), Drymoussi, Z. (Creator), Delaine-Smith, R. (Creator), Kao, A. (Creator), Laly, A. C. (Creator), Knight, M. (Creator), Philpott, M. (Creator) & Connelly, J. (Creator), The Company of Biologists Ltd, 18 Apr 2018
DOI: 10.1242/jcs.215780, http://jcs.biologists.org/content/early/2018/04/17/jcs.215780
Dataset: Data Availability Statement