A potential role for integrin signaling in mechanoelectrical feedback

Abstract

Certain forms of heart disease involve gross morphological changes to the myocardium that alter its hemodynamic loading conditions. These changes can ultimately lead to the increased deposition of extracellular matrix (ECM) proteins, such as collagen and fibronectin, which together work to pathologically alter the myocardium’s bulk tissue mechanics. In addition to changing the mechanical properties of the heart, this maladaptive remodeling gives rise to changes in myocardium electrical conductivity and synchrony since the tissue’s mechanical properties are intimately tied to its electrical characteristics. This phenomenon, called mechanoelectrical coupling (MEC), can render individuals affected by heart disease arrhythmogenic and susceptible to sudden cardiac death (SCD). The underlying mechanisms of MEC have been attributed to various processes, including the action of stretch activated channels and changes in troponin C-Ca2+ binding affinity. However, changes in the heart post infarction or due to congenital myopathies are also accompanied by shifts in the expression of various molecular components of cardiomyocytes, including the mechanosensitive family of integrin proteins. As transmembrane proteins, integrins mechanically couple the ECM with the intracellular cytoskeleton and have been implicated in mediating ion homeostasis in various cell types, including neurons and smooth muscle. Given evidence of altered integrin expression in the setting of heart disease coupled with the associated increased risk for arrhythmia, we argue in this review that integrin signaling contributes to MEC. In light of the significant mortality associated with arrhythmia and SCD, close examination of all culpable mechanisms, including integrin-mediated MEC, is necessary.

Surface Chemistry and Microtopography of Parylene C Films Control the Morphology and Microtubule Density of Cardiac Myocytes

“…31 A second possibility is that there is a different ECM deposition and characteristics on Parylene membranes of different thickness; this results in varied activation of cellular signalling pathways through transmembrane integrin-like mediators. 32 Finally, the degree of adhesion of cells on the substrate can differentially regulate mechanosensitive responses to cell contraction with consequent cytoskeletal rearrangement. 33 All these possibilities will be investigated in future experiments involving cell-cell interactions and measurements of contractility together with further assessment of signalling pathways involved in intercellular signalling.…”

Discovery and Characterization of a Potent and Specific Peptide Ligand Targeting Endothelial Progenitor Cells and Endothelial Cells for Tissue Regeneration

“…THP-1 monocytes play important roles in inflammation in the injured area and also express α 4 β 1 integrin. 38 After 2 h of incubation, the results showed that LXY30 bound only to HCECs (Figure 1A,d), but not to HECFCs or to THP-1 monocytes (Figure 1A,a,g). LLP2A bound to both HECFCs and THP-1 monocytes (Figure 1A,b,h) but not to HCECs (Figure 1A,e).…”

Dissecting the mechanical behavior of neuronal microcompartments by combining magnetic tweezers and protein micropatterns

“…It has been proposed that cytoskeleton damage is due to pathological Ca ++ entry following stress-induced mechanoporation [21] . Recently, several studies have shown that transmembrane integrins, which establish a physical link between neuronal cytoskeleton to the extracellular matrix (ECM) [22] , are important contributors to DAI by propagating mechanical forces through the cytoskeleton [23][24][25] without membrane poration. While morphological and biological damages seem to be compartmentalized to the axon, less attention has been paid to the soma.…”