arXiv subjects

Reinhard Lipowsky

Publications and source records attributed to Reinhard Lipowsky.

At least 19 recordsLinked to original sources

arXiv2021

Biohybrid active matter -- the emergent properties of cell-mediated microtransport

As society paves its way towards device miniaturization and precision medicine, micro-scale actuation and guided transport become increasingly prominent research fields with high impact in both technological and clinical contexts. In order to accomplish directed motion of micron-sized objects towards specific target sites, active biohybrid transport systems, such as motile living cells that act as smart biochemically-powered micro-carriers, have been suggested as an alternative to synthetic micro-robots. Inspired by the motility of leukocytes, we propose the amoeboid crawling of eukaryotic cells as a promising mechanism for transport of micron-sized cargoes and present an in-depth study of this novel type of composite active matter. Its transport properties result from the interactions of an active element (cell) and a passive one (cargo) and reveal an optimal cargo size that enhances the locomotion of the load-carrying cells, even exceeding their motility in the absence of cargo. The experimental findings are rationalized in terms of a biohybrid active matter theory that explains the emergent cell-cargo dynamics and enables us to derive the long-time transport properties of amoeboid micro-carries. As amoeboid locomotion is commonly observed for mammalian cells such as leukocytes, our results lay the foundations for the study of transport performance of other medically relevant cell types and for extending our findings to more advanced transport tasks in complex environments, such as tissues.

physics.bio-ph↗

arXiv2019

Force-dependent unbinding rate of molecular motors from stationary optical trap data

Molecular motors walk along filaments until they detach stochastically with a force-dependent unbinding rate. Here, we show that this unbinding rate can be obtained from the analysis of experimental data of molecular motors moving in stationary optical traps. Two complementary methods are presented, based on the analysis of the distribution for the unbinding forces and of the motor's force traces. In the first method, analytically derived force distributions for slip bonds, slip-ideal bonds, and catch bonds are used to fit the cumulative distributions of the unbinding forces. The second method is based on the statistical analysis of the observed force traces. We validate both methods with stochastic simulations and apply them to experimental data for kinesin-1.

physics.bio-ph↗

arXiv2016

Binding equilibrium and kinetics of membrane-anchored receptors and ligands in cell adhesion: insights from computational model systems and theory

The adhesion of cell membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. In this article, we review recent results from simulations and theory that lead to novel insights on how the binding equilibrium and kinetics of these proteins is affected by the membranes and by the membrane anchoring and molecular properties of the proteins. Simulations and theory both indicate that the binding equilibrium constant K2D and the on- and off-rate constants of anchored receptors and ligands in their 'two-dimensional' (2D) membrane environment strongly depend on the membrane roughness from thermally excited shape fluctuations on nanoscales. Recent theory corroborated by simulations provides a general relation between K2D} and the binding constant K3D of soluble variants of the receptors and ligands that lack the membrane anchors and are free to diffuse in three dimensions (3D).

q-bio.BM↗

arXiv2015

Binding constants of membrane-anchored receptors and ligands: a general theory corroborated by Monte Carlo simulations

Adhesion processes of biological membranes that enclose cells and cellular organelles are essential for immune responses, tissue formation, and signaling. These processes depend sensitively on the binding constant K2D of the membrane-anchored receptor and ligand proteins that mediate adhesion, which is difficult to measure in the 'two-dimensional' (2D) membrane environment of the proteins. An important problem therefore is to relate K2D} to the binding constant K3D} of soluble variants of the receptors and ligands that lack the membrane anchors and are free to diffuse in three dimensions (3D). In this article, we present a general theory for the binding constants K2D and K3D of rather stiff proteins whose main degrees of freedom are translation and rotation, along membranes and around anchor points 'in 2D', or unconstrained 'in 3D'. The theory generalizes previous results by describing how K2D depends both on the average separation and thermal nanoscale roughness of the apposing membranes, and on the length and anchoring flexibility of the receptors and ligands. Our theoretical results for the ratio K2D/K3D of the binding constants agree with detailed results from Monte Carlo simulations without any data fitting, which indicates that the theory captures the essential features of the 'dimensionality reduction' due to membrane anchoring. In our Monte Carlo simulations, we consider a novel coarse-grained model of biomembrane adhesion in which the membranes are represented as discretized elastic surfaces, and the receptors and ligands as anchored molecules that diffuse continuously along the membranes and rotate at their anchor points.

q-bio.BM↗

arXiv2015

Binding kinetics of membrane-anchored receptors and ligands: molecular dynamics simulations and theory

The adhesion of biological membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. Central questions are how the binding kinetics of these proteins is affected by the membranes and by the membrane anchoring of the proteins. In this article, we (i) present detailed data for the binding of membrane-anchored proteins from coarse-grained molecular dynamics simulations, and (ii) provide a theory that describes how the binding kinetics depends on the average separation and thermal roughness of the adhering membranes, and on the anchoring, lengths, and length variations of the proteins. An important element of our theory is the tilt of bound receptor-ligand complexes and transition-state complexes relative to the membrane normals. This tilt results from an interplay of the anchoring energy and rotational entropy of the complexes and facilitates the formation of receptor-ligand bonds at membrane separations smaller than the preferred separation for binding. In our simulations, we have considered both lipid-anchored and transmembrane receptor and ligand proteins. We find that the binding equilibrium constant and binding on-rate constant of lipid-anchored proteins are considerably smaller than the binding constant and on-rate constant of rigid transmembrane proteins with identical binding domains.

q-bio.BM↗

arXiv2015

The role of membrane curvature for the wrapping of nanoparticles

Cellular internalization of nanoparticles requires the full wrapping of the nanoparticles by the cell membrane. This wrapping process can occur spontaneously if the adhesive interactions between the nanoparticles and the membranes are sufficiently strong to compensate for the cost of membrane bending. In this article, we show that the membrane curvature prior to wrapping plays a key role for the wrapping process, besides the size and shape of the nanoparticles that have been investigated in recent years. For membrane segments that initially bulge away from nanoparticles by having a mean curvature of the same sign as the mean curvature of the particle surface, we find strongly stable partially wrapped states that can prevent full wrapping. For membrane segments that initially bulge towards the nanoparticles, in contrast, partially wrapped states can constitute a significant energetic barrier for the wrapping process.

q-bio.SC↗

arXiv2014

Semiflexible polymer rings on topographically and chemically structured surfaces

We investigate morphologies of semiflexible polymer rings, such as circular DNA, which are adsorbed onto topographically or chemically structured substrate surfaces. We classify all equilibrium morphologies for two striped surface structures, (i) topographical surface grooves and (ii) chemically structured surface domains. For both types of stripes, we find four equilibrium shapes: a round toroidal and a confined elongated shape as well as two shapes containing bulges. We determine the complete bifurcation diagram of these morphologies as a function of their contour length and the ratio of adhesive strength to bending rigidity. For more complex geometries consisting of several stripes we find a cascade of transitions between elongated shapes. Finally, we compare our findings to ring condensation by attractive interactions.

cond-mat.soft↗

arXiv2014

Cooperative wrapping of nanoparticles by membrane tubes

The bioactivity of nanoparticles crucially depends on their ability to cross biomembranes. Recent simulations indicate the cooperative wrapping and internalization of spherical nanoparticles in tubular membrane structures. In this article, we systematically investigate the energy gain of this cooperative wrapping by minimizing the energies of the rotationally symmetric shapes of the membrane tubes and of membrane segments wrapping single particles. We find that the energy gain for the cooperative wrapping of nanoparticles in membrane tubes relative to their individual wrapping as single particles strongly depends on the ratio of the particle radius and the range of the particle-membrane adhesion potential. For a potential range of the order of one nanometer, the cooperative wrapping in tubes is highly favorable for particles with a radius of tens of nanometers and intermediate adhesion energies, but not for particles that are significantly larger.

cond-mat.soft↗

arXiv2012

Non-isomorphic nucleation pathways arising from morphological transitions of liquid channels

Motivated by unexpected morphologies of the emerging liquid phase (channels, bulges, droplets) at the edge of thin, melting alkane terraces, we propose a new heterogeneous nucleation pathway. The competition between bulk and interfacial energies and the boundary conditions determine the growth and shape of the liquid phase at the edge of the solid alkane terraces. Calculations and experiments reveal a "pre-critical" shape transition (channel-to-bulges) of the liquid before reaching its critical volume along a putative shape-conserving path. Bulk liquid emerges from the new shape, and depending on the degree of supersaturation, the new pathway may have two, one, or zero energy barriers. The findings are broadly relevant for many heterogeneous nucleation processes because the novel pathway is induced by common, widespread surface topologies (scratches, steps, etc.).

physics.chem-ph↗

arXiv2012

Wetting-induced budding of vesicles in contact with several aqueous phases

Osmotic deflation of vesicles enclosing two liquid phases can lead to bulging of one of the phases from the vesicle body. This budding process is preceded by a complete to partial wetting transition of one of the liquid phases on the membrane and depends on the membrane tensions and the tension of the interface between the enclosed liquid phases. These tensions dominate in different morphology regimes, the crossover of which initiates the budding process. In addition, the degree of budding can be controlled by aspiration via micropipettes. We also demonstrate that the budding direction can be reversed if there are two external phases in contact with the vesicle.

cond-mat.soft↗

arXiv2011

Droplet-Induced Budding Transitions of Membranes

Motivated by recent experiments on biomimetic membranes exposed to several aqueous phases, we theoretically study the morphology of a membrane in contact with a liquid droplet formed via aqueous phase separation. We concentrate on membranes with negligible spontaneous curvature. At small droplet volume, bending energy dominates and the droplet is only partially wrapped by the membrane. At large volume, this configuration can become unstable and undergo a discontinuous transition to a state, in which the droplet is (almost) completely wrapped by the membrane. A morphology diagram, showing the parameter region where such budding transition occurs, is constructed as a function of the membrane tension and the intrinsic contact angle of the liquid with the membrane. The effects of spontaneous curvature are discussed qualitatively.

cond-mat.soft↗

arXiv2011

Persistence length of semiflexible polymers and bending rigidity renormalization

The persistence length of semiflexible polymers and one-dimensional fluid membranes is obtained from the renormalization of their bending rigidity. The renormalized bending rigidity is calculated using an exact real-space functional renormalization group transformation based on a mapping to the one-dimensional Heisenberg model. The renormalized bending rigidity vanishes exponentially at large length scales and its asymptotic behaviour is used to define the persistence length. For semiflexible polymers, our result agrees with the persistence length obtained using the asymptotic behaviour of tangent correlation functions. Our definition differs from the one commonly used for fluid membranes, which is based on a perturbative renormalization of the bending rigidity.

cond-mat.stat-mech↗

arXiv2011

Coupling of actin hydrolysis and polymerization: Reduced description with two nucleotide states

The polymerization of actin filaments is coupled to the hydrolysis of adenosine triphosphate (ATP), which involves both the cleavage of ATP and the release of inorganic phosphate. We describe hydrolysis by a reduced two-state model with a cooperative cleavage mechanism, where the cleavage rate depends on the state of the neighboring actin protomer in a filament. We obtain theoretical predictions of experimentally accessible steady state quantities such as the size of the ATP-actin cap, the size distribution of ATP-actin islands, and the cleavage flux for cooperative cleavage mechanisms.

cond-mat.stat-mech↗

arXiv2011

Stall force of polymerizing microtubules and filament bundles

We investigate stall force and polymerization kinetics of rigid protofilaments in a microtubule or interacting filaments in bundles under an external load force in the framework of a discrete growth model. We introduce the concecpt of polymerization cycles to describe the stochastic growth kinetics, which allows us to derive an exact expression for the stall force. We find that the stall force is independent of ensemble geometry and load distribution. Furthermore, the stall force is proportional to the number of filaments and increases linearly with the strength of lateral filament interactions. These results are corroborated by simulations, which also show a strong influence of ensemble geometry on growth kinetics below the stall force.

cond-mat.stat-mech↗

arXiv2010

Duality mapping and unbinding transitions of semiflexible and directed polymers

Directed polymers (strings) and semiflexible polymers (filaments) are one-dimensional objects governed by tension and bending energy, respectively. They undergo unbinding transitions in the presence of a short-range attractive potential. Using transfer matrix methods we establish a duality mapping for filaments and strings between the restricted partition sums in the absence and the presence of a short-range attraction. This allows us to obtain exact results for the critical exponents related to the unbinding transition, the transition point and transition order.

cond-mat.stat-mech↗

arXiv2010

Equilibrium morphologies and effective spring constants of capillary bridges

We theoretically study the behaviour of a liquid bridge formed between a pair of rigid and parallel plates. The plates are smooth, they may either be homogeneous or decorated by circular patches of more hydrophilic domains, and they are generally not identical. We calculate the mechanical equilibrium distance of the liquid bridge as a function of liquid volume, contact angle and radius of the chemical domain. We show that a liquid bridge can be an equilibrium configuration as long as the sum of the contact angles at the two walls is larger than $180^\circ$. When comparisons are possible, our results agree well with recent analytical and molecular dynamics simulation results. We also derive the effective spring constant of the liquid bridge as it is perturbed from its equilibrium distance. The spring constant diverges when the sum of the contact angles is $180^\circ$ and is finite otherwise. The value of the spring constant decreases with increasing contact angle and volume, and the rate, at which it decreases, depends strongly on the properties of the two plates.

cond-mat.soft↗

arXiv2010

Segregation of receptor-ligand complexes in cell adhesion zones: Phase diagrams and role of thermal membrane roughness

The adhesion zone of immune cells, the 'immunological synapse', exhibits characteristic domains of receptor-ligand complexes. The domain formation is likely caused by a length difference of the receptor-ligand complexes, and has been investigated in experiments in which T cells adhere to supported membranes with anchored ligands. For supported membranes with two types of anchored ligands, MHCp and ICAM1, that bind to the receptors TCR and LFA1 in the cell membrane, the coexistence of domains of TCR-MHCp and LFA1-ICAM1 complexes in the cell adhesion zone has been observed for a wide range of ligand concentrations and affinities. For supported membranes with long and short ligands that bind to the same cell receptor CD2, in contrast, domain coexistence has been observed for a rather narrow ratio of ligand concentrations. In this article, we determine detailed phase diagrams for cells adhering to supported membranes with a statistical-physical model of cell adhesion. We find a characteristic difference between the adhesion scenarios in which two types of ligands in a supported membrane bind (i) to the same cell receptor or (ii) to two different cell receptors, which helps to explain the experimental observations. Our phase diagrams fully include thermal shape fluctuations of the cell membranes on nanometer scales, which lead to a critical point for the domain formation and to a cooperative binding of the receptors and ligands.

cond-mat.soft↗

arXiv2009

Stochastic simulations of cargo transport by processive molecular motors

We use stochastic computer simulations to study the transport of a spherical cargo particle along a microtubule-like track on a planar substrate by several kinesin-like processive motors. Our newly developed adhesive motor dynamics algorithm combines the numerical integration of a Langevin equation for the motion of a sphere with kinetic rules for the molecular motors. The Langevin part includes diffusive motion, the action of the pulling motors, and hydrodynamic interactions between sphere and wall. The kinetic rules for the motors include binding to and unbinding from the filament as well as active motor steps. We find that the simulated mean transport length increases exponentially with the number of bound motors, in good agreement with earlier results. The number of motors in binding range to the motor track fluctuates in time with a Poissonian distribution, both for springs and cables being used as models for the linker mechanics. Cooperativity in the sense of equal load sharing only occurs for high values for viscosity and attachment time.

q-bio.SC↗