Biomedical subjects

Dimitrios Vavylonis

Publications and source records attributed to Dimitrios Vavylonis.

4 recordsLinked to original sources

PubMed2006

Model of formin-associated actin filament elongation.

Formin FH2 domains associate processively with actin-filament barbed ends and modify their rate of growth. We modeled how the elongation rate depends on the concentrations of profilin and actin for four different formins. We assume that (1) FH2 domains are in rapid equilibrium among conformations that block or allow actin addition and that (2) profilin-actin is transferred rapidly to the barbed end from multiple profilin binding sites in formin FH1 domains. In agreement with previous experiments discussed below, we find an optimal profilin concentration with a maximal elongation rate that can exceed the rate of actin alone. High profilin concentrations suppress elongation, largely because free profilin displaces profilin-actin from FH1. The model supports a common polymerization mechanism for the four formin FH1FH2 constructs with differences attributed to varying parameter values. The mechanism does not require ATP hydrolysis by polymerized actin, but we cannot exclude that formins accelerate hydrolysis.

Actins↗

PubMed2005

Actin polymerization kinetics, cap structure, and fluctuations.

Polymerization of actin proteins into dynamic structures is essential to eukaryotic cell life, motivating many in vitro experiments measuring polymerization kinetics of individual filaments. Here, we model these kinetics, accounting for all relevant steps revealed by experiment: polymerization, depolymerization, random ATP hydrolysis, and release of phosphate (P(i)). We relate filament growth rates to the dynamics of ATP-actin and ADP-P(i)-actin caps that develop at filament ends. At the critical concentration of the barbed end, c(crit), we find a short ATP cap and a long fluctuation-stabilized ADP-P(i) cap. We show that growth rates and the critical concentration at the barbed end are intimately related to cap structure and dynamics. Fluctuations in filament lengths are described by the length diffusion coefficient, D. Recently Fujiwara et al. [Fujiwara, I., Takahashi, S., Takaduma, H., Funatsu, T. & Ishiwata, S. (2002) Nat. Cell Biol. 4, 666-673] and Kuhn and Pollard [Kuhn, J. & Pollard, T. D. (2005) Biophys. J. 88, 1387-1402] observed large length fluctuations slightly above c(crit), provoking speculation that growth may proceed by oligomeric rather than monomeric on-off events. For the single-monomer growth process, we find that D exhibits a pronounced peak below c(crit), due to filaments alternating between capped and uncapped states, a mild version of the dynamic instability of microtubules. Fluctuations just above c(crit) are enhanced but much smaller than those reported experimentally. Future measurements of D as a function of concentration can help identify the origin of the observed fluctuations.

Actin Cytoskeleton↗

PubMed2003

The ultrasensitivity of living polymers.

Synthetic and biological living polymers are self-assembling chains whose chain length distributions (CLDs) are dynamic. We show these dynamics are ultrasensitive: Even a small perturbation (e.g., temperature jump) nonlinearly distorts the CLD, eliminating or massively augmenting short chains. The origin is fast relaxation of mass variables (mean chain length, monomer concentration) which perturbs CLD shape variables before these can relax via slow chain growth rate fluctuations. Viscosity relaxation predictions agree with experiments on the best-studied synthetic system, alpha-methylstyrene.

Biopolymers↗

PubMed2003

Irreversibility and polymer adsorption.

Physisorption or chemisorption from dilute polymer solutions often entails irreversible polymer-surface bonding. We present a theory of the resultant nonequilibrium layers. While the density profile and loop distribution are the same as for equilibrium layers, the final layer comprises a tightly bound inner part plus an outer part whose chains make only fN surface contacts where N is chain length. The contact fractions f follow a broad distribution, P(f) approximately f(-4/5), in rather close agreement with strong physisorption experiments [H. M. Schneider, Langmuir 12, 994 (1996)]].

Journal Article↗