The cytoskeleton and the cellular transduction of mechanical strain in the heart: a special issue

Abstract

There is a fundamental requirement for all cells to communicate and process information with regard to their surroundings and this is accomplished by vast array of signals that, at its basis, are all based on four principal physical processes: electricity, force, chemical reaction, and light. Mechanical strain sensing in muscle is unique in that forces are both generated by the muscle cells itself (“insideout” pathway) as well as acted upon these cells from the exterior (“outside-in” pathway). These mechanisms are critically important in the heart to alter its form and function and meet varied hemodynamic demands. Accordingly, this special issue of Pfluger s Archiv European Journal of Physiology is focused on the cellular transduction of mechanical strain in the heart. The issue is composed of invited reviews written by world leaders in their respective fields of research. A well-known example of acute strain regulation in cardiac tissue is the Frank–Starling Law of the heart [9]. Interestingly, although this basic beat-to-beat regulatory mechanism has been appreciated for over a century, the cellular mechanisms that underlie this strain transduction system have only been identified in recent decades as being caused by (a) an immediate change in cardiac cell contractility that is secondary to changes in contractile protein Ca sensitivity [11, 12], and (b) a slower change in cardiac cell contractility that develops over the course of several beats that is secondary to changes in intracellular Ca homeostasis [1, 17]. However, the molecular mechanisms and cellular signal transduction processes that underlie these cellular regulatory systems are still under intense investigation [9]. In this issue, this area of research is reviewed by contributions from the groups of Campbell [5], Cazorla [6], Cingolani [7], Peter Kohl [2], Landesberg [23], and McDonald [16]. Cardiac muscle cells are dynamic; increased mechanical load induces a hypertrophic response, while reduced load elicits the reverse response [21]. The cellular signal transduction processes responsible for this tight, long term, regulatory system that leads to remodeling of the sarcomeric architecture in the cardiac muscle cell are varied and complex. In addition, the cardiac cell is integrated into the extracellular scaffolding and force transmission system formed by the extracellular matrix, which itself is a dynamic structure that is subject to regulation and remodeling. This rapidly expanding area of research is reviewed in this special issue by contributions from the groups of Borg [3], Kresh [13], Parker [15], and Russell [8]. Among the several cytoskeletal protein structures that play a role in the cellular transduction system, the giant sarcomeric protein titin (the “fourth filament”) is particularly intriguing. Titin’s role as the predominant contributor to passive force generation within the physiological range in striated muscle is now well established [14]. However, recent observations indicate a far greater role of this giant protein in a vast array of cellular functions, including the response to cellular strain in myofilament length dependent activation, protein turnover, hypertrophic responses, and modulation of cardiac function in cardiac pathologies such P. P. de Tombe (*) Department of Cell and Molecular Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Ave, Maywood, IL 60153-5500, USA e-mail: pdetombe@lumc.edu