Cortical dynein drives centrosome clustering in cells with centrosome amplification.

During cell division, the microtubule nucleating and organizing organelle, known as the centrosome, is a critical component of the mitotic spindle. In cells with two centrosomes, each centrosome functions as an anchor point for microtubules, leading to the formation of a bipolar spindle and progression through a bipolar cell division. When extra centrosomes are present, multipolar spindles form and the parent cell may divide into more than two daughter cells.

A Framework for Generating Radial and Surface-Oriented Regularized Stokeslets.

Error in the method of regularized Stokeslets is highly dependent on the choice of the blob or regularization function that is utilized to handle singularities in the flow. In this work, we develop a general framework to choose regularizations at the level of the vector potential via smoothing factors. We detail the derivation for radial smoothing factors and specify properties which ensure that the solution is a regularized flow satisfying the incompressible Stokes equations.

Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length.

Proper formation and maintenance of the mitotic spindle is required for faithful cell division. Although much work has been done to understand the roles of the key molecular components of the mitotic spindle, identifying the consequences of force perturbations in the spindle remains a challenge. We develop a computational framework accounting for the minimal force requirements of mitotic progression.

A Bayesian Framework to Estimate Fluid and Material Parameters in Micro-swimmer Models.

To advance our understanding of the movement of elastic microstructures in a viscous fluid, techniques that utilize available data to estimate model parameters are necessary. Here, we describe a Bayesian uncertainty quantification framework that is highly parallelizable, making parameter estimation tractable for complex fluid-structure interaction models. Using noisy in silico data for swimmers, we demonstrate the methodology's robustness in estimating fluid and elastic swimmer parameters, along with their uncertainties.

A Hybrid Model of Cartilage Regeneration Capturing the Interactions Between Cellular Dynamics and Porosity.

To accelerate the development of strategies for cartilage tissue engineering, models are necessary to investigate the interactions between cellular dynamics and the local microenvironment. We use a discrete framework to capture the individual behavior of cells, modeling experiments where cells are seeded in a porous scaffold or hydrogel and over the time course of a month, the scaffold slowly degrades while cells divide and synthesize extracellular matrix constituents. The movement of cells and the ability to proliferate is a function of the local porosity, defined as the volume fraction of fluid in the surrounding region.

A computational reaction-diffusion model for biosynthesis and linking of cartilage extracellular matrix in cell-seeded scaffolds with varying porosity.

Cartilage tissue engineering is commonly initiated by seeding cells in porous materials such as hydrogels or scaffolds. Under optimal conditions, the resulting engineered construct has the potential to fill regions where native cartilage has degraded or eroded. Within a cell-seeded scaffold supplied by nutrients and growth factors, extracellular matrix accumulation should occur concurrently with scaffold degradation.

Emergent three-dimensional sperm motility: coupling calcium dynamics and preferred curvature in a Kirchhoff rod model.

Changes in calcium concentration along the sperm flagellum regulate sperm motility and hyperactivation, characterized by an increased flagellar bend amplitude and beat asymmetry, enabling the sperm to reach and penetrate the ovum (egg). The signalling pathways by which calcium increases within the flagellum are well established. However, the exact mechanisms of how calcium regulates flagellar bending are still under investigation.

Swimming speeds of filaments in viscous fluids with resistance.

Many microorganisms swim in a highly heterogeneous environment with obstacles such as fibers or polymers. To better understand how this environment affects microorganism swimming, we study propulsion of a cylinder or filament in a fluid with a sparse, stationary network of obstructions modeled by the Brinkman equation. The mathematical analysis of swimming speeds is investigated by studying an infinite-length cylinder propagating lateral or spiral displacement waves.

Nonlinear dynamics of a rotating elastic rod in a viscous fluid.

The dynamics of an elastic rod in a viscous fluid at zero Reynolds number is investigated when the bottom end of the rod is tethered at a point in space and rotates at a prescribed angular frequency, while the other part of the rod freely moves through the fluid. A rotating elastic rod, which is intrinsically straight, exhibits three dynamical motions: twirling, overwhirling, and whirling. The first two motions are stable, whereas the last motion is unstable.

Compartment calcium model of frog skeletal muscle during activation.

Skeletal muscle contraction is triggered by a rise in calcium (Ca(2+)) concentration in the myofibrillar space. The objective of this study was to develop a voltage dependent compartment model of Ca(2+) dynamics in frog skeletal muscle fibers. The compartment model corresponds to the myofibrillar space (MS) and a calcium store, the sarcoplasmic reticulum (SR).

Fluid dynamic model of invertebrate sperm chemotactic motility with varying calcium inputs.

In a marine environment, invertebrate sperm are able to adjust their trajectory in response to a gradient of chemical factors released by the egg in a process called chemotaxis. In response to this chemical factor, a signaling cascade is initiated that causes an increase in intracellular calcium (Ca(2+)). This increase in Ca(2+) causes the sperm flagellar curvature to change, and a change in swimming direction ensues.

Coupling biochemistry and hydrodynamics captures hyperactivated sperm motility in a simple flagellar model.

Hyperactivation in mammalian sperm is characterized by highly asymmetrical waveforms and an increase in the amplitude of flagellar bends. It is important for the sperm to be able to achieve hyperactivated motility in order to reach and fertilize the egg. Calcium (Ca(2+)) dynamics are known to play a large role in the initiation and maintenance of hyperactivated motility.

A model of CatSper channel mediated calcium dynamics in mammalian spermatozoa.

CatSpers are calcium (Ca(2+)) channels that are located along the principal piece of mammalian sperm flagella and are directly linked to sperm motility and hyperactivation. It has been observed that Ca(2+) entry through CatSper channels triggers a tail to head Ca(2+) propagation in mouse sperm, as well as a sustained increase of Ca(2+) in the head. Here, we develop a mathematical model to investigate this propagation and sustained increase in the head.

Anti-CD3 x anti-epidermal growth factor receptor (EGFR) bispecific antibody redirects T-cell cytolytic activity to EGFR-positive cancers in vitro and in an animal model.

Purpose: Targeting epidermal growth factor receptor (EGFR) overexpressed by many epithelial-derived cancer cells with anti-EGFR monoclonal antibodies (mAb) inhibits their growth. A limited number of clinical responses in patients treated with the anti-EGFR mAb, (cetuximab), may reflect variability in EGFR type or signaling in neoplastic cells. This study combines EGFR-targeting with the non-MHC-restricted cytotoxicity of anti-CD3 activated T cells (ATC) to enhance receptor-directed cytotoxicity.