Developmental biophysics

Main text

Developmental biophysics, the application of physical concepts and methods to the investigation of developmental processes in biology, is a broad field covering all aspects of biophysics, from experiments to theory, from molecules to cells, tissues, and organisms, and across all kingdoms of life. However, this wide scope, which makes it fascinating, also renders it very challenging. The complex environment that covers multiple spatial and temporal scales places demands on measurements, and the interpretation of results can be difficult. The developmental biophysicist faces multiple challenges: measurements in whole organisms exhibit lower signal-to-noise ratios than what can be reached in isolated in vitro studies, reducing experimental precision; the assumption of simple binary and high-affinity interactions that are tested in vitro can often not be made in the complex environment of developing tissues, making experimental planning and interpretations challenging; and the connection of events over multiple scales from the molecular scale to cellular outcomes to tissue and organism development is nontrivial and, arguably, has rarely been achieved if at all. It is, thus, not uncommon to discover that measurement outcomes differ significantly between in vitro experiments or cell culture investigations and in vivo measurements. Despite such difficulties, it is important to unravel biophysical mechanisms in living organisms, and such questions can often not be addressed in simpler systems. Therefore, developmental biophysics, despite its challenges, is one of the essential frontiers of biophysics, which promises a new understanding of the processes of life and an understanding of ourselves.

Biophysical methods and theory have progressed considerably in recent years, providing new avenues to overcome the challenges posed by exploring living systems. We are now in a position to measure at the single-molecule level in organisms, observe events at multiple scales, and computationally analyze outcomes to connect molecular processes to organism-wide events. In this special issue, we present a group of articles that cover experiment and theory, a wide range of techniques, and several model systems to harness the unique possibilities of tissue and animal models to, piece by piece, lead to a better understanding of developmental processes.

The special issue starts with a review of how one can infer mathematical relationships from observations (1). Although this seems to be the obvious and general approach that we take as scientists to interpret our experiments, the article by Seim and Grill focuses on inference from observations with no or limited perturbations. As the authors discuss, this is important not only because perturbations can often have unintended effects that make interpretation questionable but also because pure observational data can contain sufficient information to enable the inference of interaction networks when using the appropriate inference methods. The article by Falco et al. (2) uses experimental observations and Bayesian inference to produce a model of cell migration and dynamics that predicts cell cycle regulation independent of tissue crowding.

Three articles in this issue address the general question of how morphogens distribute in space and time in a graded fashion to elicit concentration-dependent cell responses to guide embryonic development (3,4,5). Interestingly, the first two works use a combination of electron and fluorescence microscopy to be able to investigate interactions at multiple scales. Gupta et al. (3) demonstrate how Fgf8 can bind to both an intercellular and a cellular membrane-bound pool of heparan sulfate proteoglycans with low affinity. These interactions fine-tune Fgf8 gradients and cell receptor binding, controlling cell type identity. Zhu et al. (4) use the combination of local high-resolution electron microscopy and large field-of-view observations by light microscopy to construct an in silico model of the zebrafish brain. Simulations in this computer model demonstrate that hindered diffusion-driven transport can explain morphogen gradient formation. A third article, by Zhang et al. (5), investigates morphogens in Drosophila embryos by using the full range of single-molecule fluorescence spectroscopy methods to measure mobility, from single-particle tracking over fluorescence correlation spectroscopy to fluorescence recovery after photobleaching (5). They demonstrate that Bicoid and Capicua, a transcriptional activator and repressor, respectively, show similar action mechanisms through oligomerization despite their different functions.

Several articles address the influence of external factors in systems from the slime mold to nematodes, fruit flies, mice, and plants. Hayashida et al. (6) investigate the role of cell size in cell-to-cell signaling, suggesting that larger cells adjust their signaling to smaller cells to homogenize signaling. Borne and Weiss (7) characterize how compressive forces influence development of the nematode embryo, demonstrating the robustness and simplicity of the developmental program. Niosi et al. (8) discuss the role of gut microbiota in neural development in the so-called gut-brain axis. Interestingly, they hint at the role of tissue mechanics as a new element involved in gut-brain communication, studying kismet, a risk gene for neurodevelopmental disorders. de Plater et al. (9) measure the influence of adhesion molecules on embryonic compaction in mice, showing how cell-cell adhesion is strengthened during compaction by the extension of adhesion rings.

This special issue also explores the relationship between patterning and cell mechanics. Ramos et al. (10) investigate how auxin signaling and tissue mechanics control root growth and development. Using computation and experiments, the authors propose a model of the role of auxin signaling on growth and its impact on tissue mechanics, leading to lateral root initiation. Tlili et al. (11) develop a minimal model of cell matching to explain how cells patterned with different adhesion molecules can reliably align. They apply this to the developing Drosophila heart and demonstrate that a single parameter (representing the balance between adhesion and elasticity) can explain a large array of mutant data in heart formation. Using quantitative live imaging and fluorescence recovery after photobleaching, Easa et al. (12) show that the Fat4 intracellular domain is important for the turnover and stability of Fat4/Dchs1 transmembrane proteins, which are associated with planar cell polarity. Their work demonstrates how morphological changes and tissue plasticity can be achieved despite the presence of an extremely stable boundary complex during development.

The issue also includes two articles providing theoretical and experimental methods that can provide new insights into the functioning of molecular complexes (13,14). Kubo and Okada (13) use coarse-grain molecular dynamics simulations to understand the mechanism of a molecular complex. Deutz et al. (14) describe a nanodisc-based extraction method applied to nematodes that allows resolving interactions of signaling complexes involved in cell polarization during development that are not detectable by other methods.

This collection of articles provides a glimpse of the wide scope of organisms studied in developmental biology, from slime molds to animals and plants, and the methodology used, from single-molecule studies and various microscopies to data analysis, as well as how progress in biophysical techniques is driving insights into the complex world of multicellular systems. We are looking forward to seeing more developments in all aspects of developmental biophysics to further our understanding of the complex systems of life.

Editor: Vasanthi Jayaraman.