Biomedical subjects

Udo Seifert

Publications and source records attributed to Udo Seifert.

7 recordsLinked to original sources

PubMed2005

Force-induced de-adhesion of specifically bound vesicles: strong adhesion in competition with tether extraction.

A theoretical study of the thermodynamic equilibrium between force-induced tether formation and the adhesion of vesicles mediated by specific ligand-receptor interactions has been performed. The formation of bonds between mobile ligands in the vesicle and immobile receptors on the substrate is examined within a thermodynamic approximation. The shape of a vesicle pulled with a point force is calculated within a continuous approach. The two approaches are merged self-consistently by the use of the effective adhesion potential produced by the collective action of the bonds. As a result, the shapes of the vesicle and the tether, as well as the number of formed bonds in the contact zone, are determined as a function of the force, and approximate analytic expressions for them are provided. The de-adhesion process is characterized by the construction of a phase diagram that is a function of the density of the ligands in the vesicle, the surface coverage by receptors, the ligand-receptor binding affinity, and the reduced volume of the vesicle. In all cases, the phase diagram contains three regions separated by two nonintersecting lines of critical forces. The first is the line of onset forces associated with a second-order shape transition from a spherical cap to a tethered vesicle. The second line is attributed to the detachment forces at which a first-order unbinding transition from a tethered shape to a free vesicle occurs.

Ligands↗

PubMed2005

Antagonist-induced deadhesion of specifically adhered vesicles.

By use of a model system consisting of giant vesicles adhering to flat substrates, we identified, both experimentally and theoretically, two new control mechanisms for antagonist-induced deadhesion. Adhesion is established by specific binding of surface-grafted E-selectin and vesicle-carrying oligosaccharide Lewis(X). Deadhesion is achieved by controlled titration of monoclonal antibodies against E-selectin. The first mechanism is characterized by a considerable retraction of the contact zone resulting in a loss of contact area between the vesicle and the substrate. Within the developed theoretical framework, the observed equilibrium state is understood as a balance between the spreading pressure of the vesicle and the antagonist-induced lateral pressure at the edge of the contact zone. In the second mechanism, the antibodies induce unbinding by penetrating the contact zone without significantly affecting its size. This process reveals the decomposition of the adhesion zone into microdomains of tight binding separated by strongly fluctuating sections of the membrane. Both experiment and theory show a sigmoidal decrease of the number of bound ligands as a function of the logarithm of antagonist concentration. The work presented herein also provides a new method for the determination of the receptor binding affinity of either the surface-embedded ligands or the competing antagonist molecules.

Animals↗

PubMed2005

Entropy production along a stochastic trajectory and an integral fluctuation theorem.

For stochastic nonequilibrium dynamics like a Langevin equation for a colloidal particle or a master equation for discrete states, entropy production along a single trajectory is studied. It involves both genuine particle entropy and entropy production in the surrounding medium. The integrated sum of both Delatas(tot) is shown to obey a fluctuation theorem (exp([-Deltas(tot) = 1 for arbitrary initial conditions and arbitrary time-dependent driving over a finite time interval.

Journal Article↗

PubMed2005

Effective adhesion strength of specifically bound vesicles.

A theoretical approach has been undertaken in order to model the thermodynamic equilibrium of a 3D vesicle adhering to a flat substrate. The vesicle is treated in a canonical description with a fixed number of sites. A finite number of these sites are occupied by mobile ligands that are capable of interacting with a discrete number of receptors immobilized on the substrate. Explicit consideration of the bending energy of the vesicle shape has shown that the problem of the vesicle shape can be decoupled from the determination of the optimum allocation of ligands over the vesicle. The allocation of bound and free ligands in the vesicle can be determined as a function of the size of the contact zone, the ligand-receptor binding strength, and the concentration of the system constituents. Several approximate solutions for different regions of system parameters are determined and in particular, the distinction between receptor- and ligand-dominated equilibria is found to be important. The crossover between these two types of solutions is found to occur at a critical size of the contact zone. The presented approach enables the calculation of the effective adhesion strength of the vesicle and thus permits meaningful comparisons with relevant experiments as well as connecting the presented model with the proven success of the continuum approach for modeling the shapes of adhering vesicles. The behavior of the effective adhesion strength is analyzed in detail and several approximate expressions for it are given.

Adhesiveness↗

PubMed2004

Distribution of work in isothermal nonequilibrium processes.

Diffusive motion in an externally driven potential is considered. It is shown that the distribution of work required to drive the system from an initial equilibrium state to another is Gaussian for slow but finite driving. Our result is obtained by projection method techniques exploiting a small parameter defined as the switching rate between the two states of the system. The exact solution for a simple model system shows that such an expansion may fail in higher orders, since the mean and the variance following from the exact distribution show nonanalytic behavior.

Journal Article↗

PubMed2004

Probing molecular free energy landscapes by periodic loading.

Single molecule pulling experiments provide information about interactions in biomolecules that cannot be obtained by any other method. However, the reconstruction of the molecule's free energy profile from the experimental data is still a challenge, in particular, for the unstable barrier regions. We propose a new method for obtaining the full profile by introducing a periodic ramp and using Jarzynski's relation for obtaining equilibrium quantities from nonequilibrium data. Our simulated experiments show that this method delivers significant more accurate data than previous methods, under the constraint of equal experimental effort.

Bacteriorhodopsins↗

PubMed2004

Pulling tethers from adhered vesicles.

The competition between adhesion and tether formation in bound vesicles is investigated. A theoretical model is developed in which tethers are induced by the application of a pulling force to the top of a strongly adhered vesicle. A critical onset force is identified where the tether spontaneously appears as part of a first order shape transition. Further growth of the tether initiates a detachment process that culminates in a continuous unbinding of the vesicle at a finite detachment force. Both critical forces, as well as all shape parameters, are calculated as a function of the reduced volume and the strength of adhesive potential.

Cell Adhesion↗