ABSTRACT
Important Not to Get StiffConnective tissues fibroblasts are continuously subjected to a range of dynamic forces that change the mechanical state of the tissue through either cell-cell interactions, cell-ECM interactions, or ECM-ECM interactions [1]. Different mechanical signals come from a variety of sources, including gravity, muscle movement, breathing, and heart beat [1,2]. In this chapter, we will concentrate on two mechanical signals that dominate the behavior of fibroblastic cells: stretch and ECM stiffness. Although how fibroblasts mechanosense and subsequently interpret mechanical signals is not entirely understood, it has been established that
several components orchestrate mechanotransduction events in concert, including the opening of mechanosensitive ions channels, initiation of integrin-mediated mechanical pathways, binding of cell-cell linkages, and force-induced exposure to otherwise cryptic peptide sequences [3,4]. Tissue deformations, experienced by residing fibroblasts as stretch, are not only essential for the physical maintenance and management of tissues, but also guide biological responses. Responses to stretch include changes in cell shape, reorientation [5], increases in proliferation rates [6], alteration of migratory behavior [7], and changes in the expression and synthesis of a variety of contractile and regulatory proteins [6]. Stretch is particularly important for fibroblasts within connective tissues of mechanically active organs such as heart, lung, tendon, and skin. It is the task of fibroblasts to creating a stable and well-structured ECM optimized to resist external loads [8]. Therefore when mechanical loading becomes heightened or compromised from trauma, abnormal loading, or pathological onset, the way in which resident cells respond in terms of ECM reorganization and production becomes a key component in dictating healthy or diseased outcomes [9]. A paradigm for load-induced physiological and pathological ECM remodeling is the development of cardiac fibrosis in conditions of chronic hypertension [10].
