First, the universal features of polarizing cells are listed, and details of the Mori-Jilkine wave-pinning model are assembled and discussed biologically and mathematically. A short review of thelocal pulse analysis is provided to indicate the usefulness of this method of analysis. Then, I discuss the survey of polarizing cells from a paper by Jilkine and LEK (2011) that appeared in PLoS Comput Biol 7(4): e1001121. Here, common and distinct attributes of different cell types and of several models for cell polarization are compared. The responses of models to a set of computational perturbations mimicking stimuli protocols are described.
This lecture introduces the topic of 2D cell motility simulations, but focuses on one specific method, the CPM (as implemented by Maree et al in Bull Math Biol (2006), 68(5):1169-1211 and PLoS Comput Biol (2012) 8(3): e1002402). I explain the details of the method, the biological facts that were included (signaling from GTPases and phosphoinositides to actin assembly and myosin contraction). I illustrate typical results, and then discuss some of the technical aspects of the method, emphasizing its link to the (previously discussed) Metropolis-Hastings algorithm. I also show how Stan Maree was able to chose CPM parameters to phenomenologically mimic the known relationship between actin filament ends and cell protrusion speed.
In this lecture I describe a model by Grimm et al (2003) Eur Biophys J 32: 563-577. The authors ask what processes might account for a parabolic density profile of actin seen across the front edge of a keratocyte. In an elegant coupled PDE model, they show that right and left growing actin filaments, competing for the actin branching complex Arp2/3 have solutions with the appropriate profile. I here
consider one of the cases, that of local competition and slow capping of filaments, where the equations are fully analytically solvable in closed form.
Fragments of fish pigment cells can form and center aggregates of
pigment granules by dynein-motor-driven transport along a
self-organized radial array of microtubules (MTs). I will present a
quantitative model that describes pigment aggregation and MT-aster
self-organization and the subsequent centering of both structures.
The model is based on the observations that MTs are immobile and
treadmill, while dynein-motor-covered granules have the ability to
nucleate MTs. From assumptions based on experimental observations,
I'll derive partial integro-differential equations describing the
coupled granule-MT interaction. Analysis explains the mechanism of
aster self-organization as a positive feedback loop between motor
aggregation at the MT minus ends and MT nucleation by motors.
Furthermore, the centering mechanism is explained as a global
geometric bias in the cell established by spontaneously-nucleated
microtubules. Numerical simulations lend additional support to the
analysis. The model sheds light on role of polymer dynamics and
polymer-motor interactions in cytoskeletal organization.
Polarization, where cells segregate specific factors to distinct domains, is a fundamental and evolutionarily conserved biological process. Polarizing cells often rely on the same toolkit of proteins and lipids, including actin, myosin, microtubules and the Par and Rho protein families. In this talk, I will present experimental and theoretical work demonstrating the importance of Par protein oligomerization for stable spatial segregation in early embryos of C. elegans. I will discuss some current research directions in my lab, including the incorporation of Rho proteins into our theoretical and experimental frameworks.