Chemotaxis is typically modeled in the context of cellular motion towards a static, exogenous source of chemoattractant. Here, we propose a time-dependent mechanism of chemotaxis in which a self-propelled particle ({it e.g.}, a cell) releases a chemi
cal that diffuses to fixed particles (targets) and signals the production of a second chemical by these targets. The particle then moves up concentration gradients of this second chemical, analogous to diffusive echolocation. When one target is present, we describe probe release strategies that optimize travel of the cell to the target. In the presence of multiple targets, the one selected by the cell depends on the strength and, interestingly, on the frequency of probe chemical release. Although involving an additional chemical signaling step, our chemical ``pinging hypothesis allows for greater flexibility in regulating target selection, as seen in a number of physical or biological realizations.
Enveloped viruses enter host cells either through endocytosis, or by direct fusion of the viral membrane envelope and the membrane of the host cell. However, some viruses, such as HIV-1, HSV-1, and Epstein-Barr can enter a cell through either mechani
sm, with the choice of pathway often a function of the ambient physical chemical conditions, such as temperature and pH. We develop a stochastic model that describes the entry process at the level of binding of viral glycoprotein spikes to cell membrane receptors and coreceptors. In our model, receptors attach the cell membrane to the viral membrane, while subsequent binding of coreceptors enables fusion. The model quantifies the competition between fusion and endocytotic entry pathways. Relative probabilities for each pathway are computed numerically, as well as analytically in the high viral spike density limit. We delineate parameter regimes in which fusion or endocytosis is dominant. These parameters are related to measurable and potentially controllable quantities such as membrane bending rigidity and receptor, coreceptor, and viral spike densities. Experimental implications of our mechanistic hypotheses are proposed and discussed.
We investigate the mechanisms of histone sliding and detachment with a stochastic model that couples thermally-induced, passive histone sliding with active motor-driven histone unwrapping. Analysis of a passive loop or twist defect-mediated histone s
liding mechanism shows that diffusional sliding is enhanced as larger portions of the DNA is peeled off the histone. The mean times to histone detachment and the mean distance traveled by the motor complex prior to histone detachment are computed as functions of the intrinsic speed of the motor. Fast motors preferentially induce detachment over sliding. However, for a fixed motor speed, increasing the histone-DNA affinity (and thereby decreasing the passive sliding rate) increases the mean distance traveled by the motor.
We propose a stochastic process wherein molecular transport is mediated by asymmetric nucleation of domains on a one-dimensional substrate. Track-driven mechanisms of molecular transport arise in biophysical applications such as Holliday junction pos
itioning and collagenase processivity. In contrast to molecular motors that hydrolyze nucleotide triphosphates and undergo a local molecular conformational change, we show that asymmetric nucleation of hydrolysis waves on a track can also result in directed motion of an attached particle. Asymmetrically cooperative kinetics between ``hydrolyzed and ``unhydrolyzed states on each lattice site generate moving domain walls that push a particle sitting on the track. We use a novel fluctuating-frame, finite-segment mean field theory to accurately compute steady-state velocities of the driven particle and to discover parameter regimes which yield maximal domain wall flux, leading to optimal particle drift.
