Prabhakar, R. | bioRxiv Science

bioRxiv2020

Role of cell polarity dynamics and motility in pattern formation due to contact dependent signalling

A key challenge in biology is to understand how spatiotemporal patterns and structures arise during the development of an organism. An initial aggregate of spatially uniform cells develops and forms the differentiated structures of a fully developed organism. On the one hand, contact-dependent cell-cell signalling is responsible for generating a large number of complex, self-organized, spatial patterns in the distribution of the signalling molecules. On the other hand, the motility of cells coupled with their polarity can independently lead to collective motion patterns that depend on mechanical parameters influencing tissue deformation, such as cellular elasticity, cell-cell adhesion and active forces generated by actin and myosin dynamics. Although modelling efforts have, thus far, treated cell motility and cell-cell signalling separately, experiments in recent years suggest that these processes could be tightly coupled. Hence, in this paper, we study how the dynamics of cell polarity and migration influence the spatiotemporal patterning of signalling molecules. Such signalling interactions can occur only between cells that are in physical contact, either directly at the junctions of adjacent cells or through cellular protrusional contacts. We present a vertex model which accounts for contact-dependent signalling between adjacent cells and between non-adjacent neighbours through long protrusional contacts that occur along the orientation of cell polarization. We observe a rich variety of spatiotemporal patterns of signalling molecules that is influenced by polarity dynamics of the cells, relative strengths of adjacent and non-adjacent signalling interactions, range of polarized interaction, signalling activation threshold, relative time scales of signalling and polarity orientation, and cell motility. Though our results are developed in the context of Delta-Notch signalling, they are sufficiently general and can be extended to other contact dependent morpho-mechanical dynamics.

biophysics↗

bioRxiv2020

Flagellar energetics from high-resolution imaging of beating patterns in tethered mouse sperm

While much is known about the microstructure of sperm flagella, the mechanisms behind the generation of flagellar beating patterns by the axoneme are still not fully understood. We demonstrate a technique for investigating the energetics of flagella or cilia. We record the planar beating of tethered wildtype and Crisp2-knockout mouse sperm at high-speed and high-resolution and extract centerlines using digital image processing techniques. We accurately reconstruct beating waveforms using a Chebyshev-polynomial based Proper Orthogonal Decomposition of the centerline tangent-angle profiles. External hydrodynamic forces and the internal resistance from the passive flagellar material are calculated from the observed kinematics of the beating patterns using a Soft, Internally-Driven Kirchhoff-Rod (SIDKR) model. Energy conservation is employed to further compute the flagellar energetics. We thus obtain the distribution of mechanical power exerted by the dynein motors without any further assumptions about mechanisms regulating axonemal function. We find that, in both the mouse genotypes studied, a large proportion of the mechanical power exerted by the dynein motors is dissipated internally, within the passive structures of the flagellum and by the motors themselves. This internal dissipation is considerably greater than the hydrodynamic dissipation in the aqueous medium outside. The net power input from the dynein motors in sperm from Crisp2-knockout mice is significantly smaller than in corresponding wildtype samples. The reduced power is correlated with slower beating and smaller amplitudes. These measurements of flagellar energetics indicate that the ion-channel regulating cysteine-rich secretory proteins (CRISPs) may also be involved in regulating mammalian sperm motility.

cell biology↗