Cell shape: effects on gene expression and signaling

Abstract

The perception of biophysical forces (mechanosensation) and their conversion into chemical signals (mechanotransduction) are fundamental biological processes. They are connected to hypertrophic and atrophic cellular responses, and defects in these processes have been linked to various diseases, especially in the cardiovascular system. Although cardiomyocytes generate, and are exposed to, considerable hemodynamic forces that affect their shapes, until recently, we did not know whether cell shape affects gene expression. However, new single-cell trapping strategies, followed by single-cell RNA sequencing, to profile the transcriptomes of individual cardiomyocytes of defined geometrical morphotypes have been developed that are characteristic for either normal or pathological (afterload or preload) conditions. This paper reviews the recent literature with regard to cell shape and the transcriptome and provides an overview of this newly emerging field, which has far-reaching implications for both biology, disease, and possibly therapy.

Keywords: Cell geometry,; Cell shape,; Gene expression,; Heart failure,; Mechanosensation,; Mechanotransduction.

Fig. 1

Schematic of reaction-diffusion-advection (RAD) model. External or internal stress causes strain. The membrane receptors that can bind to arbitrary molecules A are denoted R in the unbound form and AR in the bound form. The binding process is $A+R\genfrac{}{}{0pt}{}{k_{\mathit{on}}}{\stackrel{\leftharpoonup }{\stackrel{\rightharpoonup }{k_{\mathit{off}}}}}\mathit{AR}$. A is free to diffuse in any direction, whereas R is limited to diffuse along the membrane plane, with the diffusion coefficients of D_A and D_R, respectively. The concentration of molecules A varies due to diffusion and reaction but also varies due to advection (shown by velocity vector field v_A). Advection could be a consequence of strain or cell contraction (e.g., in CMs)

Fig. 2

Any changes in cell shape, either globally (such as size, volume, AR, or geometry) or locally (such as protrusion or invagination of local membranes), cause substantial consequences from modifying cellular architecture to altering gene expression

Fig. 3

A COMSOL program was designed to mathematically simulate the advection of an arbitrary molecule A, floating in one sarcomere of a CM towards the sarcolemma. The advection is due to contraction of CM. For a CM to contract, the sarcomere must shorten from 2.2 to 1.6 μm. a One CM was assumed as a cylinder, consisting of several symmetric sarcomeres. Since sarcomeres are similar repeating units, one contracting sarcomere was modeled. Moreover, it was assumed that the liquid inside the sarcomere is incompressible. b The finite-element mesh was generated to divide the model into small elements, over which a set of Navier-Stokes equations were solved. c When the sarcomere contracts, the pressure from the liquid is exerted to the contracting z-disks. The exerted pressure in different parts of the z-disk is shown by color-coded contours. d The arrows are the velocity vector (advection), caused by shortening the sarcomere. The arrow length is proportional to the magnitude of velocity