Multi-scale mechanics from molecules to morphogenesis

Abstract

Dynamic mechanical processes shape the embryo and organs during development. Little is understood about the basic physics of these processes, what forces are generated, or how tissues resist or guide those forces during morphogenesis. This review offers an outline of some of the basic principles of biomechanics, provides working examples of biomechanical analyses of developing embryos, and reviews the role of structural proteins in establishing and maintaining the mechanical properties of embryonic tissues. Drawing on examples we highlight the importance of investigating mechanics at multiple scales from milliseconds to hours and from individual molecules to whole embryos. Lastly, we pose a series of questions that will need to be addressed if we are to understand the larger integration of molecular and physical mechanical processes during morphogenesis and organogenesis.

Biology meets physics: Reductionism and multi-scale modeling of morphogenesis

“…Like the steel example, some aspects of biological structures require continuum models whereas others have to take into account the structural diversity of and stochastic relations between the discrete interacting cells and molecules (Lesne, 2013). In biology, researchers face the additional challenge that different integrated processes operate also on different time-scales, from milliseconds to hours, days or even years (Davidson et al, 2009). As Newman et al (2011, p. 313) clarify, developmental systems display both discrete and continuous aspects, depending on the specific spatial and temporal scale of the specific developmental processes.…”

“…The establishment of tissue boundaries and geometrical structures during morphogenesis is mediated and stabilized by interconnected adhesions between cells and the extracellular matrix (ECM). Adhesions fix cells and cell populations in structures with varying degrees of freedom for bending and motility (Davidson et al 2009). The proteins involved in adhesion serve both mechanical and signaling roles through force-transmission and mechano-transduction, i.e., conversion of a mechanical stimulus into chemical cues that influence biochemical pathways (see also Section 3.2).…”

“…Determining the stiffness of the epithelium and surrounding tissues (Figure 3d) involves finding values for material parameters, such as Young's Modulus and various tensor fields. Importantly, defining such parameters for the viscous materials of biological tissues involves multi-scale analysis, because the characteristic of macroscale physical forces acting on the integrated effects of the dynamics of cell populations are practically invisible at the molecular scale (Davidson et al, 2009). Tractable models of various epithelial movements, however, require ignoring extreme lower-scale (molecular or genetic) details.…”

“…As mentioned in Section 2.1, because the physical forces act on the integrated effects of cell populations, biomechanical modeling of the viscous materials requires macroscale measurements and models (Davidson et al, 2009;Davidson, 2012). One possible objection is that the examined macroscale properties are merely background conditions for biological explanations.…”

“…While these terms nicely capture the difference between cell-autonomous "programmed" mechanisms and trajectories towards physically constrained states, the terminology may lead to an underestimation of the explanatory relevance of the latter. 17 Many developmental biologists, including Davidson himself (personal communication), are therefore concerned with the way that this terminology may downplay the explanatory power of physical aspects of development (see also Davidson et al, 2009;Love, 2015). The concern is that physical aspects are mainly taken to describe but not explain.…”