Mechanobiology of Epithelia From the Perspective of Extracellular Matrix Heterogeneity

Abstract

Understanding the complexity of the extracellular matrix (ECM) and its variability is a necessary step on the way to engineering functional (bio)materials that serve their respective purposes while relying on cell adhesion. Upon adhesion, cells receive messages which contain both biochemical and mechanical information. The main focus of mechanobiology lies in investigating the role of this mechanical coordination in regulating cellular behavior. In recent years, this focus has been additionally shifted toward cell collectives and the understanding of their behavior as a whole mechanical continuum. Collective cell phenomena very much apply to epithelia which are either simple cell-sheets or more complex three-dimensional structures. Researchers have been mostly using the organization of monolayers to observe their collective behavior in well-defined experimental setups in vitro. Nevertheless, recent studies have also reported the impact of ECM remodeling on epithelial morphogenesis in vivo. These new concepts, combined with the knowledge of ECM biochemical complexity are of key importance for engineering new interactive materials to support both epithelial remodeling and homeostasis. In this review, we summarize the structure and heterogeneity of the ECM before discussing its impact on the epithelial mechanobiology.

Laminin-defined Mechanical Status Modulates Retinal Pigment Epithelium Functionality

“…Next, we were curious to know if the quantified mechanical gradient of RPE finds a correlation with the distribution of mechanical and biochemical cues within the Bruch’s membrane. In the epithelial ECM, mechanical cues are mostly determined by the interstitial matrix composition and crosslinking (Kozyrina et al , 2020). Therefore, we use confocal microscopy and immunofluorescence staining to quantify the amount of collagen type I and elastin present only at Bruch’s membrane level.…”

“…In a homeostatic state, these mechanical features are maintained in a preferred range for optimal activity, also known as tissue mechanical homeostasis (Eichinger et al , 2021). One of the main players in defining the mechanical homeostasis of tissues is its extracellular matrix (ECM) composition (Humphrey et al , 2014; Kozyrina et al , 2020).…”

A Model of Using the Asymmetric Polydopamine Thin Film for Mimicking Epithelial Folding In Vitro

“…It should be noted that this intrinsic stiffness and the thickness of the PDA film showed similarity in comparison to the human native basal membrane (≈1.0 MPa, ≈100 nm in thickness). [ 35 ] As evidenced by the SEM (Figure 1A), the PDA film displayed high flexibility and could be deformed without cracking, which makes the PDA film of high potential for mimicking the epithelial wrinkling and folding. Our result confirmed that the freestanding PDA film could support the growth of the epithelial cells and was able to be deformed by the cells (Figure 6D), which may be attributed to the cell‐generated forces, such as cell‐cell and cell‐substrate adhesion forces as well as forces resulting from the plasma membrane tension and actomyosin contractility.…”

Kinesin-3 and kinesin-1 motors direct basement membrane protein secretion to a basal sub-region of the basolateral plasma membrane in epithelial cells

“…We imagine that the formation of ectopic BM protein networks between cells would be detrimental to any epithelial tissue undergoing cellular rearrangements. These would include processes like cell division and cell extrusion that are required for tissue growth and homeostasis, as well as processes like cell intercalation and apical constriction that underlie changes in tissue shape (Kozyrina et al, 2020). Given that BM assembly and epithelial morphogenesis often coincide during development (Jayadev and Sherwood, 2017; Walma and Yamada, 2020), we propose that kinesin-based transport of BM proteins toward the basal surface may provide a general mechanism to ensure that that these two key aspects of epithelial development do not interfere with one another.…”