Biomedical subjects

U S Schwarz

Publications and source records attributed to U S Schwarz.

10 recordsLinked to original sources

PubMed2006

Efficiency of initiating cell adhesion in hydrodynamic flow.

We theoretically investigate the efficiency of initial binding between a receptor-coated sphere and a ligand-coated wall in linear shear flow. The mean first passage time for binding decreases monotonically with increasing shear rate. Above a saturation threshold of the order of a few 100 receptor patches, the binding efficiency is enhanced only weakly by increasing their number and size, but strongly by increasing their height. This explains why white blood cells in the blood flow adhere through receptor patches localized to the tips of microvilli, and why malaria-infected red blood cells form elevated receptor patches (knobs).

Biomechanical Phenomena↗

PubMed2005

Effect of poisson ratio on cellular structure formation.

Mechanically active cells in soft media act as force dipoles. The resulting elastic interactions are long ranged and favor the formation of strings. We show analytically that due to screening, the effective interaction between strings decays exponentially, with a decay length determined only by geometry. Both for disordered and ordered arrangements of cells, we predict novel phase transitions from paraelastic to ferroelastic and antiferroelastic phases as a function of the Poisson ratio.

Cellular Structures↗

PubMed2004

Stability of adhesion clusters under constant force.

We solve the stochastic equations for a cluster of parallel bonds with shared constant loading, rebinding, and the completely dissociated state as an absorbing boundary. In the small force regime, cluster lifetime grows only logarithmically with bond number for weak rebinding, but exponentially for strong rebinding. Therefore rebinding is essential to ensure physiological lifetimes. The number of bonds decays exponentially with time for most cases, but in the intermediate force regime a small increase in loading can lead to much faster decay. This effect might be used by cell-matrix adhesions to induce signaling events through cytoskeletal loading.

Cell Adhesion↗

PubMed2004

Elastic interactions of active cells with soft materials.

Anchorage-dependent cells collect information on the mechanical properties of the environment through their contractile machineries and use this information to position and orient themselves. Since the probing process is anisotropic, cellular force patterns during active mechanosensing can be modeled as anisotropic force contraction dipoles. Their buildup depends on the mechanical properties of the environment, including elastic rigidity and prestrain. In a finite sized sample, it also depends on sample geometry and boundary conditions through image strain fields. We discuss the interactions of active cells with an elastic environment and compare it to the case of physical force dipoles. Despite marked differences, both cases can be described in the same theoretical framework. We exactly solve the elastic equations for anisotropic force contraction dipoles in different geometries (full space, half space, and sphere) and with different boundary conditions. These results are then used to predict optimal position and orientation of mechanosensing cells in soft material.

Animals↗

PubMed2003

Cell organization in soft media due to active mechanosensing.

Adhering cells actively probe the mechanical properties of their environment and use the resulting information to position and orient themselves. We show that a large body of experimental observations can be consistently explained from one unifying principle, namely that cells strengthen contacts and cytoskeleton in the direction of large effective stiffness. Using linear elasticity theory to model the extracellular environment, we calculate optimal cell organization for several situations of interest and find excellent agreement with experiments for fibroblasts, both on elastic substrates and in collagen gels: cells orient in the direction of external tensile strain; they orient parallel and normal to free and clamped surfaces, respectively; and they interact elastically to form strings. Our method can be applied for rational design of tissue equivalents. Moreover, our results indicate that the concept of contact guidance has to be reevaluated. We also suggest that cell-matrix contacts are up-regulated by large effective stiffness in the environment because, in this way, build-up of force is more efficient.

Cell Adhesion↗

PubMed2002

Elastic interactions of cells.

Biological cells in soft materials can be modeled as anisotropic force contraction dipoles. The corresponding elastic interaction potentials are long ranged (approximately 1/r3 with distance r) and depend sensitively on elastic constants, geometry, and cellular orientations. On elastic substrates, the elastic interaction is similar to that of electric quadrupoles in two dimensions and for dense systems leads to aggregation with herringbone order on a cellular scale. Free and clamped surfaces of samples of finite size introduce attractive and repulsive corrections, respectively, which vary on the macroscopic scale. Our theory predicts cell reorientation on stretched elastic substrates.

Cell Communication↗

PubMed2002

Calculation of forces at focal adhesions from elastic substrate data: the effect of localized force and the need for regularization.

Forces exerted by stationary cells have been investigated on the level of single focal adhesions by combining elastic substrates, fluorescence labeling of focal adhesions, and the assumption of localized force when solving the inverse problem of linear elasticity theory. Data simulation confirms that the inverse problem is ill-posed in the presence of noise and shows that in general a regularization scheme is needed to arrive at a reliable force estimate. Spatial and force resolution are restricted by the smoothing action of the elastic kernel, depend on the details of the force and displacement patterns, and are estimated by data simulation. Corrections arising from the spatial distribution of force and from finite substrate size are treated in the framework of a force multipolar expansion. Our method is computationally cheap and could be used to study mechanical activity of cells in real time.

Algorithms↗

PubMed2001

Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism.

The transition of cell-matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II-driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal contact formation. To dissect the mechanism of Rho-dependent induction of focal contacts and to elucidate the role of cell contractility, we applied mechanical force to vinculin-containing dot-like adhesions at the cell edge using a micropipette. Local centripetal pulling led to local assembly and elongation of these structures and to their development into streak-like focal contacts, as revealed by the dynamics of green fluorescent protein-tagged vinculin or paxillin and interference reflection microscopy. Inhibition of Rho activity by C3 transferase suppressed this force-induced focal contact formation. However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136-143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells. Force-induced formation of the focal contacts still occurred in cells subjected to myosin II and ROCK inhibition. Thus, as long as mDia1 is active, external tension force bypasses the requirement for ROCK-mediated myosin II contractility in the induction of focal contacts. Our experiments show that integrin-containing focal complexes behave as individual mechanosensors exhibiting directional assembly in response to local force.

3T3 Cells↗

PubMed2001

Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates.

Mechanical forces play a major role in the regulation of cell adhesion and cytoskeletal organization. In order to explore the molecular mechanism underlying this regulation, we have investigated the relationship between local force applied by the cell to the substrate and the assembly of focal adhesions. A novel approach was developed for real-time, high-resolution measurements of forces applied by cells at single adhesion sites. This method combines micropatterning of elastomer substrates and fluorescence imaging of focal adhesions in live cells expressing GFP-tagged vinculin. Local forces are correlated with the orientation, total fluorescence intensity and area of the focal adhesions, indicating a constant stress of 5.5 +/- 2 nNmicrom(-2). The dynamics of the force-dependent modulation of focal adhesions were characterized by blocking actomyosin contractility and were found to be on a time scale of seconds. The results put clear constraints on the possible molecular mechanisms for the mechanosensory response of focal adhesions to applied force.

Animals↗

PubMed1999

Systematic approach to bicontinuous cubic phases in ternary amphiphilic systems.

The Fourier approach and theories of space groups and color symmetries are used to systematically generate and compare bicontinuous cubic structures in the framework of a Ginzburg-Landau model for ternary amphiphilic systems. Both single and double structures are investigated; they correspond to systems with one or two monolayers in a unit cell, respectively. We show how and why single structures can be made to approach triply periodic minimal surfaces very closely, and give improved nodal approximations for G, D, I-WP, and P surfaces. We demonstrate that the relative stability of the single structures can be calculated from the geometrical properties of their interfaces only. The single gyroid G turns out to be the most stable bicontinuous cubic phase since it has the smallest porosity. The representations are used to calculate distributions of the Gaussian curvature and 2H-nuclear-magnetic-resonance band shapes for C(P), C(D), S, C(Y), and F-RD surfaces.

Journal Article↗