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While the heart is a dynamic organ and one of its major functions is to provide the organism with sufficient blood supply, the regulatory feedback systems, which allow adaptation to hemodynamic changes, remain not well understood. Our current description of mechanosensation focuses on stretch-sensitive ion channels, cytoskeletal components, structures such as the sarcomeric Z-disc, costameres, caveolae, or the concept of tensegrity, but these models appear incomplete as the remarkable plasticity of the myocardium in response to biomechanical stress and heart rate variations remains unexplained. Signaling activity at membranes depends on their geometric parameters such as surface area and curvature, which links shape to information processing. In the heart, continuous cycles of contraction and relaxation reshape membrane morphology and hence affect cardio-mechanic signaling. This article provides a brief review on current models of mechanosensation and focuses on how signaling, cardiac myocyte dynamics, and membrane shape interact and potentially give rise to a self-organized system that uses shape to sense the extra- and intracellular environment. This novel concept may help to explain how changes in frequency, and thus membrane shape, affect cardiac plasticity. One of the conclusions is that hypertrophy and associated fibrosis, which have been considered as necessary to cope with increased wall stress, can also be seen as part of complex feedback systems which use local membrane inhomogeneity in different cardiac cell types to influence whole organphysiology and which are predicted to fine-tune and thus regulate membrane-mediated signaling.

Muscle LIM protein (MLP, also known as cysteine rich protein 3 (CSRP3, CRP3)) is a muscle-specific-expressed LIM-only protein. It consists of 194 amino-acids and has been described initially as a factor involved in myogenesis (Arber et al. Cell 79:221–231, 1994). MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393–403, 1997). At this time, this was the first genetically altered animal model to develop this devastating disease. Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674–2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78–85, 2006; Geier et al. Circulation 107:1390–1395, 2003; Hershberger et al. Clin Transl Sci 1:21–26, 2008; Knöll et al. Cell 111:943–955, 2002; Knöll et al. Circ Res 106:695–704, 2010; Mohapatra et al. Mol Genet Metab 80:207–215, 2003). Although considerable efforts have been undertaken to unravel the underlying molecular mechanisms—how MLP mutations, either in model organisms or in the human setting cause these diseases are still unclear. In contrast, only precise knowledge of the underlying molecular mechanisms will allow the development of novel and innovative therapeutic strategies to combat this otherwise lethal condition. The focus of this review will be on the function of MLP in cardiac mechanosensation and we shall point to possible future directions in MLP research.

Erratum to: Pflugers Arch - Eur J Physiol (2014) 466:1093–1099 DOI 10.1007/s00424-014-1468-4

Mechanosensation and mechanotransduction are fundamental aspects of biology, but the link between physical stimuli and biological responses remains not well understood. The perception of mechanical stimuli, their conversion into biochemical signals, and the transmission of these signals are particularly important for dynamic organs such as the heart. Various concepts have been introduced to explain mechanosensation at the molecular level, including effects on signalosomes, tensegrity, or direct activation (or inactivation) of enzymes. Striated muscles, including cardiac myocytes, differ from other cells in that they contain sarcomeres which are essential for the generation of forces and which play additional roles in mechanosensation. The majority of cardiomyopathy causing candidate genes encode structural proteins among which titin probably is the most important one. Due to its elastic elements, titin is a length sensor and also plays a role as a tension sensor (i.e., stress sensation). The recent discovery of titin mutations being a major cause of dilated cardiomyopathy (DCM) also underpins the importance of mechanosensation and mechanotransduction in the pathogenesis of heart failure. Here, we focus on sarcomere-related mechanisms, discuss recent findings, and provide a link to cardiomyopathy and associated heart failure.