Mechanics of development

1. Introduction

The notion of developmental mechanics (or Entwicklungsmechanik) was pioneered by Wilhelm Roux in the late nineteenth and early twentieth centuries [1] but was almost forgotten as attention shifted towards advances in genetics and molecular biology. Developmental mechanics has undergone a quiet revival in recent years, as a growing number of developmental processes have been shown to depend on aspects of the mechanical microenvironment. In adult tissues, mechanical forces have profound effects on cell behaviour, but less is known about their roles during embryonic development. Forces are rapidly perceived by a cell, and in a developing embryo that is undergoing very dynamic changes in cell number, cell shape, cell contacts and cell migration, signals due to mechanical forces are almost certainly critical regulators of many, if not all, embryonic processes. The integration of mechanical with biochemical signals ensures that growth and morphogenesis are robust. When the development of an organ depends on mechanical forces, there are important ramifications for understanding its normal function and pathophysiology, and for recapitulating its form via tissue engineering.

In February 2018, a Theo Murphy International Scientific meeting on the ‘Mechanics of Development’ was held, with the aim of bringing together researchers focused on how mechanical forces modulate and determine specific aspects of embryonic and foetal development. This special issue highlights the research areas of the speakers at the meeting and provides a flavour of the wide range of exciting research in the area. In this Introduction, we wish to highlight the breadth and variety of the research field and so we include recent papers from the broader literature. Research groups across the world are investigating how mechanical forces affect the development of every major organ in the body, including the cardiovascular and lymphatic systems [2–7], the musculoskeletal system [3,8–13], the brain [14,15], the eye [16], the neural tube [17,18], the skin [19], the gut [20–23] and the lung and mammary gland [24–26], in addition to the processes that shape the very early embryo, such as gastrulation [27], and mechanotransduction at the cellular or sub-cellular levels during development [28–31]. A range of animal models are being used, including chick [8–10], mouse [8,11] fly [28,32–34] and zebrafish [12–35] in addition to—or alongside—computational models [2,12,13,36,37]. Researchers in the field come from a range of backgrounds including developmental biology, biomechanics, bioengineering, cell signalling, anatomy, computational sciences and biophysics and therefore use a range of techniques. These include atomic force microscopy (AFM) and tissue cutting to measure forces [38–40], live imaging to analyse cellular behaviours [35], and micropatterned islands to determine how cell shape (i.e. actomyosin cytoskeletal activity) directs cell fate [41]. However, all researchers have in common a key focus on the role of mechanical forces in embryonic or foetal development.

A key discussion topic that emerged at the meeting was the fact that the interplay between mechanical forces and development has different meanings for different researchers and research areas. At the largest length scale, there are external ‘applied’ or ‘active’ forces (due to, for example, muscle activity, fluid flow or vessel contraction) encompassing most studies of the development of the musculoskeletal system (including [8–11,12,13] in this issue), and many investigations of cardiovascular development (e.g. [2]). A length scale down, there are forces due to pressure differences or physical constraints (e.g. cortical folding constrained by skull, lung branching), as covered by Jaslove & Nelson [26] and Garcia et al. [15]. Then there are the forces (pre-stresses) that are inherently within tissues and structures, which may change over development and may direct aspects of it, as covered by Chevalier [23] in this issue, and others [20,42]. At the cell-, rather than tissue-, level, mechanical forces can affect aspects such as cell shape, organization and orientation, as described by Tetley & Mao [28] and Bagnat et al. [12]. Finally, we get down to mechanotransduction, at the cell organelle or gene levels, as described by Inbger [31]. For many processes, the exact mechanotransduction pathways are still very unclear. Modulation of canonical Wnt signalling activity was also a topic of interest at the meeting. The key effector of this pathway, Armadillo /β-catenin, is both a membrane-associated protein and transcriptional cofactor and has been shown to play critical roles in mechanotransduction in developmental systems [8,43,44]. A classic example is the evolutionarily conserved role of Armadillo/β-catenin in response to force (in this case, stretch) during mesoderm induction in both Drosophila and zebrafish [45]. Other potential transcriptional or co-transcriptional mechanotransduction effectors include Yorkie/Yap/Taz [46–48], Myocardin-related transcription factor and serum response factor (reviewed in [49]).

The growing, multi-disciplinary areas of developmental biomechanics and mechanobiology are ripe for expansion. The research is capitalizing on the application of new technologies to embryonic cells, tissues and organs, including AFM, optic and magnetic tweezers, high-resolution time-lapse imaging, bioreactor culture systems, microfabrication and other tissue engineering advances and is also timely based on the explosion in our understanding of signalling pathways involved in integrating cells' response to the local environment. Greater understanding could lead to advances in a range of broader fields, particularly developmental biology, bioengineering and tissue engineering. We hope that readers will enjoy this special edition of Philosophical Transactions B, which sheds light on this growing and interdisciplinary field.

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Authors' contributions

All authors contributed actively to the writing of the paper and have approved the final version of the manuscript.

Competing interests

We declare we have no competing interests.

Funding

N.C.N. is funded by the European Research Council under the European Union's Seventh Framework Programme (ERC Grant agreement no. (336306)). P.F.W. is funded by the BBSRC (London Interdisciplinary Doctoral Programme (LIDo) BB/M022544/1, BB/K008668/1). C.M.N. is funded in part by a Faculty Scholars Award from the Howard Hughes Medical Institute.