Mechanical stretch and stiffness effects on fibroblasts: regulators of matrix remodeling and disease

CRISP Seminar

Dr. Jenna Balestrini
Postdoctoral Associate, Yale School of Medicine

"Mechanical stretch and stiffness effects on fibroblasts: regulators of matrix remodeling and disease"

Virtually all connective tissues are mechanically loaded in the body, and these loads provide cues that regulate fundamental physiological processes such as tissue growth and maintenance, wound healing, and angiogenesis. This talk will focus on two distinct yet fundamental areas of connective tissue mechanobiology: 1) how fibroblasts respond to mechanical strain in terms of functional matrix remodeling, and 2) how matrix stiffness can guide fibroblasts towards quiescent or fibrotic (i.e, myofibroblastic) phenotypes. Previous studies investigating strain-dependent fibroblast behavior provide fundamental information regarding the response of cells to mechanical stimulation; however, these studies do not apply complex deformation patterns that occur in connective tissue nor do they provide physiologically relevant stiffness conditions to investigate. Strain patterns in vivo are anisotropic with local gradients of strain; these non-uniformities in strain distribution can be especially pronounced in tissues undergoing clinical intervention or during disease onset (e.g., formation of fibrotic foci in the lung). Previous research including establishing functional dose-response curves of matrix remodeling metrics in response to strain, and the development of an experimental system to produce non-uniform strain patterns for studying the effect of strain magnitude, anisotropy, and gradients on cells will be highlighted. To investigate the matrix stiffness-dependent cell behavior we have also developed novel systems to isolate and culture fibroblasts over several passages on soft silicone substrates that model healthy and diseased lung tissue. Using this system, we will first determine if mechanically preconditioning fibroblasts on pathological levels of stiffness permanently activates them towards the highly synthetic, contractile and myofibroblast cell phenotype.

Monday, December 3, 2012
10:00 am – 11:00 am
Becton Lab 227
15 Prospect Street, New Haven, CT