Biology subjects

Frey, E.

Publications and source records attributed to Frey, E..

25 records · Page 2Linked to original sources

bioRxiv2019

Quasi-periodic migration of single cells on short microlanes

Cell migration on microlanes represents a suitable and simple platform for the exploration of the molecular mechanisms underlying cell cytoskeleton dynamics. Here, we report on the quasi-periodic movement of cells confined in stripe-shaped microlanes. We observe persistent polarized cell shapes and directed pole-to-pole motion within the microlanes. Cells depolarize at one end of a given microlane, followed by delayed repolarization towards the opposite end. We analyze cell motility via the spatial velocity distribution, the velocity frequency spectrum and the reversal time as a measure for depolarization and spontaneous repolarization of cells at the microlane ends. The frequent encounters of a boundary in the stripe geometry provides a robust framework for quantitative investigations of the cytoskeleton protrusion and repolarization dynamics. In a first advance to rigorously test physical models of cell migration, we find that the statistics of the cell migration is recapitulated by a Cellular Potts model with a minimal description of cytoskeleton dynamics. Using LifeAct-GFP transfected cells and microlanes with differently shaped ends, we show that the local deformation of the leading cell edge in response to the tip geometry can locally either amplify or quench actin polymerization, while leaving the average reversal times unaffected.

biophysics↗

bioRxiv2019

A mechanistic view of collective filament motion in active nematic networks

Protein filament networks are structures crucial for force generation and cell shape. A central open question is how collective filament dynamics emerges from interactions between individual network constituents. To address this question we study a minimal but generic model for a nematic network where filament sliding is driven by the action of motor proteins. Our theoretical analysis shows how the interplay between viscous drag on filaments and motor-induced forces governs force propagation through such interconnected filament networks. We find that the ratio between these antagonistic forces establishes the range of filament interaction, which determines how the local filament velocity depends on the polarity of the surrounding network. This force propagation mechanism implies that the polarity-independent sliding observed in Xenopus egg extracts, and in-vitro experiments with purified components, is a consequence of a large force propagation length. We suggest how our predictions can be tested by tangible in vitro experiments whose feasibility is assessed with the help of simulations and an accompanying theoretical analysis.

biophysics↗

bioRxiv2019

Design of biochemical pattern forming systems from minimal motifs

Although molecular self-organization and pattern formation are key features of life, only very few pattern-forming biochemical systems have been identified that can be reconstituted and studied in vitro under defined conditions. A systematic understanding of the underlying mechanisms is often hampered by multiple interactions, conformational flexibility and other complex features of the pattern forming proteins. Because of its compositional simplicity of only two proteins and a membrane, the MinDE system from Escherichia coli has in the past years been invaluable for deciphering the mechanisms of spatiotemporal self-organization in cells. Here we explored the potential of reducing the complexity of this system even further, by identifying key functional motifs in the effector MinE that could be used to design pattern formation from scratch. In a combined approach of experiment and quantitative modeling, we show that starting from a minimal MinE-MinD interaction motif, pattern formation can be obtained by adding either dimerization or membrane-binding motifs. Moreover, we show that the pathways underlying pattern formation are recruitment-driven cytosolic cycling of MinE and recombination of membrane-bound MinE, and that these differ in their in vivo phenomenology.

biophysics↗

bioRxiv2019

Stochastic Yield Catastrophes and Robustness in Self-Assembly

A guiding principle in self-assembly is that, for high production yield, nucleation of structures must be significantly slower than their growth. However, details of the mechanism that impedes nucleation are broadly considered irrelevant. Here, we analyze self-assembly into finite-sized target structures employing mathematical modeling. We investigate two key scenarios to delay nucleation: (i) by introducing a slow activation step for the assembling constituents and, (ii) by decreasing the dimerization rate. These scenarios have widely different characteristics. While the dimerization scenario exhibits robust behavior, the activation scenario is highly sensitive to demographic fluctuations. These demographic fluctuations ultimately disfavor growth compared to nucleation and can suppress yield completely. The occurrence of this stochastic yield catastrophe does not depend on model details but is generic as soon as number fluctuations between constituents are taken into account. On a broader perspective, our results reveal that stochasticity is an important limiting factor for self-assembly and that the specific implementation of the nucleation process plays a significant role in determining the yield.

biophysics↗

bioRxiv2019

Bridging the gap between single cell migration and collective dynamics

A wealth of experimental data relating to the emergence of collective cell migration as one proceeds from the behavioral dynamics of small cohorts of cells to the coordinated migratory response of cells in extended tissues is now available. Integrating these findings into a mechanistic picture of cell migration that is applicable across such a broad range of system sizes constitutes a crucial step towards a better understanding of the basic factors that determine the emergence of collective cell motion. Here we present a cellular-automaton-based modeling framework, which focuses on the integration of high-level cell functions and their concerted effect on cellular migration patterns. In particular, we adopt a top-down approach to incorporate a coarse-grained description of cell polarity and its response to mechanical cues, and address the impact of cell adhesion on collective migration in cell groups. We demonstrate that the model faithfully reproduces typical cell shapes and movements down to the level of single cells, yet is computationally efficient enough to allow for the simulation of (currently) up to [O](104) cells. To develop a mechanistic picture that illuminates the relationship between cell functions and collective migration, we present a detailed study of small groups of cells in confined circular geometries, and discuss the emerging patterns of collective motion in terms of specific cellular properties. Finally, we apply our computational model at the level of extended tissues, and investigate stress and velocity distributions, as well as front morphologies, in expanding cellular sheets.

biophysics↗

bioRxiv2018

Can a flux-based mechanism explain positioning of protein clusters in a three-dimensional cell geometry?

The plane of bacterial cell division must be precisely positioned. In the bacterium Myxococcus xanthus, the proteins PomX and PomY form a large cluster, which is tethered to the nucleoid by the ATPase PomZ and moves in a stochastic, but biased manner towards midcell, where it initiates cell division. Previously, a positioning mechanism based on the fluxes of PomZ on the nucleoid was proposed. However, the cluster dynamics was analyzed in a reduced, one-dimensional geometry. Here we introduce a mathematical model that accounts for the three-dimensional shape of the nucleoid, such that nucleoid-bound PomZ dimers can diffuse past the cluster without interacting with it. Using stochastic simulations, we find that the cluster still moves to and localizes at midcell. Redistribution of PomZ by diffusion in the cytosol is essential for this cluster dynamics. Our mechanism also positions two clusters equidistantly on the nucleoid. We conclude that a flux-based mechanism allows for cluster positioning in a biologically realistic three-dimensional cell geometry.

biophysics↗

bioRxiv2018

PAR protein activation-deactivation cycles stabilize long-axis polarization in C. elegans

In the Caenorhabditis elegans zygote, PAR protein patterns, driven by mutual anatagonism, determine the anterior-posterior axis and facilitate the redistribution of proteins for the first cell division. Yet, the factors that determine the selection of the polarity axis remain unclear. We present a reaction-diffusion model in realistic cell geometry, based on biomolecular reactions and accounting for the coupling between membrane and cytosolic dynamics. We find that the kinetics of the phosphorylation-dephosphorylation cycle of PARs and the diffusive protein fluxes from the cytosol towards the membrane are crucial for the robust selection of the anterior-posterior axis for polarisation. The local ratio of membrane surface to cytosolic volume is the main geometric cue that initiates pattern formation, while the choice of the long-axis for polarisation is largely determined by the length of the aPAR-pPAR interface, and mediated by processes that minimise the diffusive fluxes of PAR proteins between cytosol and membrane.

biophysics↗