Christopher Miles

University of California, Irvine | UCI · Department of Mathematics

We propose and analyze a mathematical model of cargo transport by non-processive molecular motors. In our model, the motors change states by random discrete events (corresponding to stepping and binding/unbinding), while the cargo position follows a stochastic differential equation (SDE) that depends on the discrete states of the motors. The result...

Many types of cells require the ability to pinpoint the location of an external stimulus from the arrival of diffusing signaling molecules at cell-surface receptors. How does the organization (number and spatial configuration) of these receptors shape the limit of a cell’s ability to infer the source location? In the idealized scenario of a spheric...

Despite the well-established role of actin polymerization as a driving mechanism for cell protrusion, upregulated actin polymerization alone does not initiate protrusions. Using a combination of theoretical modeling and quantitative live-cell imaging experiments, we show that local depletion of actin-membrane links is needed for protrusion initiati...

Intracellular forces shape cellular organization and function. One example is the mitotic spindle, a cellular machine consisting of multiple chromosomes and centrosomes which interact via dynamic microtubule filaments and motor proteins, resulting in complicated spatially dependent forces. For a cell to divide properly, it is important for the spin...

Proper segregation of chromosomes during mitosis depends on "amphitelic attachments"-load-bearing connections of sister kinetochores to the opposite spindle poles via bundles of microtubules, termed as the "K-fibers." Current models of spindle assembly assume that K-fibers arise largely from stochastic capture of microtubules, which occurs at rando...

The self-organization of cells relies on the profound complexity of protein-protein interactions. Challenges in directly observing these events have hindered progress toward understanding their diverse behaviors. One notable example is the interaction between molecular motors and cytoskeletal systems that combine to perform a variety of cellular fu...

Many imaging techniques for biological systems -- like fixation of cells coupled with fluorescence microscopy -- provide sharp spatial resolution in reporting locations of individuals at a single moment in time but also destroy the dynamics they intend to capture. These snapshot observations contain no information about individual trajectories, but...

Many imaging techniques for biological systems -- like fixation of cells coupled with fluorescence microscopy -- provide sharp spatial resolution in reporting locations of individuals at a single moment in time but also destroy the dynamics they intend to capture. These snapshot observations contain no information about individual trajectories, but...

Delays and stochasticity have both served as crucially valuable ingredients in mathematical descriptions of control, physical and biological systems. In this work, we investigate how explicitly dynamical stochasticity in delays modulates the effect of delayed feedback. To do so, we consider a hybrid model where stochastic delays evolve by a continu...

Transient bonds between fast linkers and slower particles are widespread in physical and biological systems. Despite their diverse structure and function, a commonality is that the linkers diffuse on timescales much faster compared to the overall motion of the particles they bind to. This limits numerical and theoretical approaches that need to res...

Collective motion of locally interacting agents is found ubiquitously throughout nature. The inability to probe individuals has driven longstanding interest in the development of methods for inferring the underlying interactions. In the context of heterogeneous collectives, where the population consists of individuals driven by different interactio...

Delays and stochasticity have both served as crucially valuable ingredients in mathematical descriptions of control, physical, and biological systems. In this work, we investigate how explicitly dynamical stochasticity in delays modulates the effect of delayed feedback. To do so, we consider a hybrid model where stochastic delays evolve by a contin...

Transient bonds between fast linkers and slower particles are widespread in physical and biological systems. In spite of their diverse structure and function, a commonality is that the linkers diffuse on timescales much faster compared to the overall motion of the particles they bind to. This limits numerical and theoretical approaches that need to...

Actin networks adapt to resistance by becoming denser. A recent investigation shows that this mechanosensation relies on a force-sensitive mechanical ratchet of capping actin filaments to reorganize the network. This and other mechanical feedback mechanisms make actin-based protrusion amazingly robust.

Intracellular forces shape cellular organization and function. One example is the mitotic spindle, a cellular machine consisting of multiple chromosomes and centrosomes which interact via dynamic microtubule filaments and motor proteins, resulting in complicated spatially dependent forces. For a cell to divide properly, is important for the spindle...

Cells constantly need to move molecules and organelles throughout their interior. RNA produced in the nucleus must be exported to then be translated into proteins. Some of these proteins must then be imported back into the nucleus. Others are packaged into membrane vesicles, which in turn must be trafficked to the plasma membrane and exocytosed fro...

The distance between fluorescent spots formed by various kinetochore proteins (delta) is commonly interpreted as a manifestation of intrakinetochore tension (IKT) caused by microtubule-mediated forces. However, large-scale changes of the kinetochore architecture (such as its shape or dimensions) may also contribute to the value of delta. To assess...

The time that it takes a diffusing particle to find a small target has emerged as a critical quantity in many systems in molecular and cellular biology. In this paper, we extend the theory for calculating this time to account for several ubiquitous biological features which have largely been ignored in the mathematics and physics literature on this...

Distance between fluorescent spots formed by various kinetochore proteins ('Delta') is proposed to reflect the level of intrakinetochore tension (IKT). However, larger-scale changes in the kinetochore architecture may also affect Delta. To test this possibility, we measure Delta in long kinetochores of Indian muntjac (IM) whose shape, size, and ori...

Cell morphogenesis employs a diversity of membrane protrusions. They are discriminated by differences in force generation. Actin polymerization is the best studied mechanism of force generation, but growing interest in how variable molecular conditions and microenvironments alter morphogenesis has revealed other mechanisms, including intracellular...

We report a minimal microtubule-based motile system displaying signatures of unconventional diffusion. The system consists of a single model cargo driven by an ensemble of N340K NCD motors along a single microtubule. Despite the absence of cytosolic or cytoskeleton complexity, the system shows complex behavior, characterized by sub-diffusive motion...

Many biological processes are initiated when diffusing extracellular reactants reach receptors on a cell membrane. Calculating this arrival rate has therefore attracted theoretical interest for decades. However, previous work has largely ignored the fact that receptors diffuse on the two-dimensional cell membrane in a process called surface or late...

We propose a general framework for studying jump-diffusion systems driven by both Gaussian noise and a jump process with state-dependent intensity. Of particular natural interest are the jump locations: the system evaluated at the jump times. However, the state-dependence of the jump rate provides direct coupling between the diffusion and jump comp...

Molecular motor proteins serve as an essential component of intracellular transport by generating forces to haul cargoes along cytoskeletal filaments. In some circumstances, two species of motors that are directed oppositely (e.g. kinesin, dynein) can be attached to the same cargo. The resulting net motion is known to be bidirectional, but the mech...