arXiv subjects

Brian A. Camley

Publications and source records attributed to Brian A. Camley.

30 records · Page 2Linked to original sources

arXiv2020

Chemotaxis in uncertain environments: hedging bets with multiple receptor types

Eukaryotic cells are able to sense chemical gradients in a wide range of environments. We show that, if a cell is exposed to a highly variable environment, it may gain chemotactic accuracy by expressing multiple receptor types with varying affinities for the same signal, as found commonly in chemotaxing cells like Dictyostelium. As environment uncertainty is increased, there is a transition between cells preferring a single receptor type and a mixture of types - hedging their bets against the possibility of an unfavorable environment. We predict the optimal receptor affinities given a particular environment. In chemotaxing, cells may also integrate their measurement over time. Surprisingly, time-integration with multiple receptor types is qualitatively different from gradient sensing by a single type -- cells may extract orders of magnitude more chemotactic information than expected by naive time integration. Our results show when cells should express multiple receptor types to chemotax, and how cells can efficiently interpret the data from these receptors.

q-bio.CB↗

arXiv2019

Motion of objects embedded in lipid bilayer membranes: advection and effective viscosity

An interfacial regularized Stokeslet scheme is presented to predict the motion of solid bodies (e.g. proteins or gel-phase domains) embedded within flowing lipid bilayer membranes. The approach provides a numerical route to calculate velocities and angular velocities in complex flow fields that are not amenable to simple Faxén-like approximations. Additionally, when applied to shearing motions, the calculations yield predictions for the effective surface viscosity of dilute rigid body-laden membranes. In the case of cylindrical proteins, effective viscosity calculations are compared to two prior analytical predictions from the literature. Effective viscosity predictions for a dilute suspension of rod-shaped objects in the membrane are also presented.

physics.bio-ph↗

arXiv2019

Hydrodynamic Effects on the Motility of Crawling Eukaryotic Cells

Eukaryotic cell motility is crucial during development, wound healing, the immune response, and cancer metastasis. Some eukaryotic cells can swim, but cells more commonly adhere to and crawl along the extracellular matrix. We study the relationship between hydrodynamics and adhesion that describe whether a cell is swimming, crawling, or combining these motions. Our simple model of a cell, based on the three-sphere swimmer, is capable of both swimming and crawling. As cell-matrix adhesion strength increases, the influence of hydrodynamics on migration diminish. Cells with significant adhesion can crawl with speeds much larger than their nonadherent, swimming counterparts. We predict that, while most eukaryotic cells are in the strong-adhesion limit, increasing environment viscosity or decreasing cell-matrix adhesion could lead to significant hydrodynamic effects even in crawling cells. Signatures of hydrodynamic effects include dependence of cell speed on the medium viscosity or the presence of a nearby substrate and the presence of interactions between noncontacting cells. These signatures will be suppressed at large adhesion strengths, but even strongly adherent cells will generate relevant fluid flows that will advect nearby passive particles and swimmers.

q-bio.CB↗

arXiv2019

Cell Motility Dependence on Adhesive Wetting

Adhesive cell-substrate interactions are crucial for cell motility and are responsible for the necessary traction that propels cells. These interactions can also change the shape of the cell, analogous to liquid droplet wetting on adhesive substrates. To address how these shape changes affect cell migration and cell speed we model motility using deformable, 2D cross-sections of cells in which adhesion and frictional forces between cell and substrate can be varied separately. Our simulations show that increasing the adhesion results in increased spreading of cells and larger cell speeds. We propose an analytical model which shows that the cell speed is inversely proportional to an effective height of the cell and that increasing this height results in increased internal shear stress. The numerical and analytical results are confirmed in experiments on motile eukaryotic cells.

physics.bio-ph↗

arXiv2017

Cell-to-cell variation sets a tissue-rheology-dependent bound on collective gradient sensing

When a single cell senses a chemical gradient and chemotaxes, stochastic receptor-ligand binding can be a fundamental limit to the cell's accuracy. For clusters of cells responding to gradients, however, there is a critical difference: even genetically identical cells have differing responses to chemical signals. With theory and simulation, we show collective chemotaxis is limited by cell-to-cell variation in signaling. We find that when different cells cooperate the resulting bias can be much larger than the effects of ligand-receptor binding. Specifically, when a strongly-responding cell is at one end of a cell cluster, cluster motion is biased toward that cell. These errors are mitigated if clusters average measurements over times long enough for cells to rearrange. In consequence, fluid clusters are better able to sense gradients: we derive a link between cluster accuracy, cell-to-cell variation, and the cluster rheology. Because of this connection, increasing the noisiness of individual cell motion can actually increase the collective accuracy of a cluster by improving fluidity.

q-bio.CB↗

arXiv2016

Crawling and turning in a minimal reaction-diffusion cell motility model: coupling cell shape and biochemistry

We study a minimal model of a crawling eukaryotic cell with a chemical polarity controlled by a reaction-diffusion mechanism describing Rho GTPase dynamics. The size, shape, and speed of the cell emerge from the combination of the chemical polarity, which controls the locations where actin polymerization occurs, and the physical properties of the cell, including its membrane tension. We find in our model both highly persistent trajectories, in which the cell crawls in a straight line, and turning trajectories, where the cell transitions from crawling in a line to crawling in a circle. We discuss the controlling variables for this turning instability, and argue that turning arises from a coupling between the reaction-diffusion mechanism and the shape of the cell. This emphasizes the surprising features that can arise from simple links between cell mechanics and biochemistry. Our results suggest that similar instabilities may be present in a broad class of biochemical descriptions of cell polarity.

physics.bio-ph↗

arXiv2015

Emergent collective chemotaxis without single-cell gradient sensing

Many eukaryotic cells chemotax, sensing and following chemical gradients. However, experiments have shown that even under conditions when single cells cannot chemotax, small clusters may still follow a gradient. This behavior has been observed in neural crest cells, in lymphocytes, and during border cell migration in Drosophila, but its origin remains puzzling. Here, we propose a new mechanism underlying this "collective guidance", and study a model based on this mechanism both analytically and computationally. Our approach posits that the contact inhibition of locomotion (CIL), where cells polarize away from cell-cell contact, is regulated by the chemoattractant. Individual cells must measure the mean attractant value, but need not measure its gradient, to give rise to directional motility for a cell cluster. We present analytic formulas for how cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. The presence of strong orientation effects provides a simple test for our theory of collective guidance.

physics.bio-ph↗

arXiv2015

Collective signal processing in cluster chemotaxis: roles of adaptation, amplification, and co-attraction in collective guidance

Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of "collective guidance" computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster's size - clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signal; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion to function. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Together, the combination of co-attraction and adaptation allows for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion.

q-bio.CB↗

arXiv2014

Calculating hydrodynamic interactions for membrane-embedded objects

A recently introduced numerical scheme for calculating self-diffusion coefficients of solid objects embedded in lipid bilayer membranes is extended to enable calculation of hydrodynamic interactions between multiple objects. The method is used to validate recent analytical predictions by Oppenheimer and Diamant [Biophys. J., 96, 3041, 2009] related to the coupled diffusion of membrane embedded proteins and is shown to converge to known near-field lubrication results as objects closely approach one another, however the present methodology also applies outside of the limiting regimes where analytical results are available. Multiple different examples involving pairs of disk-like objects with various constraints imposed on their relative motions demonstrate the importance of hydrodynamic interactions in the dynamics of proteins and lipid domains on membrane surfaces. It is demonstrated that the relative change in self-diffusion of a membrane embedded object upon perturbation by a similar proximal solid object displays a maximum for object sizes comparable to the Saffman-Delbrück length of the membrane.

cond-mat.soft↗

arXiv2014

Velocity alignment leads to high persistence in confined cells

Many cell types display random motility on two-dimensional substrates, but crawl persistently in a single direction when confined in a microchannel or on an adhesive micropattern. Does this imply that the motility mechanism of confined cells is fundamentally different from that of unconfined cells? We argue that both free- and confined- cell migration may be described by a generic model of cells as "velocity aligning" active Brownian particles previously proposed to solve a completely separate problem in collective cell migration. Our model can be mapped to a diffusive escape over a barrier and analytically solved to determine the cell's orientation distribution and repolarization rate. In quasi-one-dimensional confinement, velocity-aligning cells maintain their direction for times that can be exponentially larger than their persistence time in the absence of confinement. Our results suggest an important new connection between single- and collective- cell migration: high persistence in confined cells corresponds with fast alignment of velocity to cell-cell forces.

physics.bio-ph↗

arXiv2013

Periodic migration in a physical model of cells on micropatterns

We extend a model for the morphology and dynamics of a crawling eukaryotic cell to describe cells on micropatterned substrates. This model couples cell morphology, adhesion, and cytoskeletal flow in response to active stresses induced by actin and myosin. We propose that protrusive stresses are only generated where the cell adheres, leading to the cell's effective confinement to the pattern. Consistent with experimental results, simulated cells exhibit a broad range of behaviors, including steady motion, turning, bipedal motion, and periodic migration, in which the cell crawls persistently in one direction before reversing periodically. We show that periodic motion emerges naturally from the coupling of cell polarization to cell shape by reducing the model to a simplified one-dimensional form that can be understood analytically.

q-bio.CB↗

arXiv2011

Dynamic simulations of multicomponent lipid membranes over long length and time scales

We present a stochastic phase-field model for multicomponent lipid bilayers that explicitly accounts for the quasi-two-dimensional hydrodynamic environment unique to a thin fluid membrane immersed in aqueous solution. Dynamics over a wide range of length scales (from nanometers to microns) for durations up to seconds and longer are readily accessed and provide a direct comparison to fluorescence microscopy measurements in ternary lipid/cholesterol mixtures. Simulations of phase separation kinetics agree with experiment and elucidate the importance of hydrodynamics in the coarsening process.

cond-mat.soft↗