Tissue Morphogenesis Through Dynamic Cell and Matrix Interactions

Abstract

Multicellular organisms generate tissues of diverse shapes and functions from cells and extracellular matrices. Their adhesion molecules mediate cell-cell and cell-matrix interactions, which not only play crucial roles in maintaining tissue integrity but also serve as key regulators of tissue morphogenesis. Cells constantly probe their environment to make decisions: They integrate chemical and mechanical information from the environment via diffusible ligand- or adhesion-based signaling to decide whether to release specific signaling molecules or enzymes, to divide or differentiate, to move away or stay, or even whether to live or die. These decisions in turn modify their environment, including the chemical nature and mechanical properties of the extracellular matrix. Tissue morphology is the physical manifestation of the remodeling of cells and matrices by their historical biochemical and biophysical landscapes. We review our understanding of matrix and adhesion molecules in tissue morphogenesis, with an emphasis on key physical interactions that drive morphogenesis.

Keywords: basement membrane; cadherin; cell adhesion; extracellular matrix; integrin; interfacial tension.

Figure 1

Biophysical principles of tissue morphogenesis. (a) Each tissue explores morphology space. Directional change is determined by free energy minimization, while the speed of change is controlled by the kinetic energy. (b,c) Two theories explaining cell sorting during tissue morphogenesis. (d) Cortical tension changes when a cell attaches to another cell or matrix. (e) Jamming and unjamming transitions during tissue morphogenesis decrease or increase the kinetic energy, respectively. (f) Tissue patterning by fluid instability can be generated from reciprocal cell contraction and extracellular matrix (ECM) alignment.

Figure 2

Cell-cell adhesion mediated by classical cadherins. (a) Domain structure of classical cadherins. (b) Extracellular and intracellular interactions of cadherins. X-dimer and S-dimer are two conformations of trans dimers. (c) Cadherin dimers can cluster via cis interactions. Expansion of the adhesion surface is driven by adjacent actomyosin contraction. Abbreviations: CBD, catenin-binding domain; JMD, juxtamembrane domain.

Figure 3

Extracellular matrices and their receptors. (a) Basement membrane and interstitial matrix are two major types of extracellular matrix. (b,c) Assembly of the collagen fibril (b) or fibronectin fibril (c). (d) Components of the basement membrane. Dashed lines indicate some known interactions. (e) Matrix receptors on the cell surface and adaptor/signaling proteins binding to the cytoplasmic tail of integrins. Abbreviations: 7S, N-terminal domain with a sedimentation coefficient of 7S as a tetramer; C, C terminus; ECM, extracellular matrix; FAK, focal adhesion kinase; LG, laminin globular domain; LN, laminin N-terminal domain; N, N terminus; NC1, noncollagenous 1.