Fluid mechanics as a driver of tissue-scale mechanical signaling in organogenesis

Abstract

Purpose of review: Organogenesis is the process during development by which cells self-assemble into complex, multi-scale tissues. Whereas significant focus and research effort has demonstrated the importance of solid mechanics in organogenesis, less attention has been given to the fluid forces that provide mechanical cues over tissue length scales.

Recent findings: Fluid motion and pressure is capable of creating spatial gradients of forces acting on cells, thus eliciting distinct and localized signaling patterns essential for proper organ formation. Understanding the multi-scale nature of the mechanics is critically important to decipher how mechanical signals sculpt developing organs.

Summary: This review outlines various mechanisms by which tissues generate, regulate, and sense fluid forces and highlights the impact of these forces and mechanisms in case studies of normal and pathological development.

Keywords: birth defects; ion channels; mechanics of development; mechanotransduction; morphogenesis.

Figure 1. During organogenesis, a variety of methods are used to move fluid around throughout the lumenal compartments of diverse organs

A) Ion channels allow for fluid movement across cell layers. For example, in lung epithelium, the CFTR channel will actively transport chloride ions across the apical side of the epithelium. The elevated chloride concentration draws neutralizing sodium currents and water through the leaky cell junctions, providing a tonic pressure within the lumen. A variety of diseases can occur due to defective ion channels, which cause either too much, or not enough, fluid in organ lumen structures. B) Cilia are small microstructures found on the apical side of epithelium. They will beat in a uniform, circumferential motion to drive fluid flows. Other cells sense these different fluid flows and will change their growth accordingly. Cilia-based fluid flows are a major driver of symmetry breaking during development and organogenesis. C) Smooth muscle is found in a variety of organs during development such as the ureter and lung. Smooth muscle can contract in a peristaltic wave that moves fluid in the same direction and can influence growth patterns by regulating local fluid pressures within specific regions of the lumen. D) Mechanosensitive ion channels are able to respond to tissue scale mechanical forces such as fluid pressure or fluid flow and convert these forces into cellular signals. For example, the calcium channel TRPV4 can respond to fluid flow by allowing the influx of extracellular calcium ions that produce a variety of downstream molecular and genetic effects within the cell.