10 research outputs found
Curvature-coupling dependence of membrane protein diffusion coefficients
We consider the lateral diffusion of a protein interacting with the curvature
of the membrane. The interaction energy is minimized if the particle is at a
membrane position with a certain curvature that agrees with the spontaneous
curvature of the particle. We employ stochastic simulations that take into
account both the thermal fluctuations of the membrane and the diffusive
behavior of the particle. In this study we neglect the influence of the
particle on the membrane dynamics, thus the membrane dynamics agrees with that
of a freely fluctuating membrane. Overall, we find that this curvature-coupling
substantially enhances the diffusion coefficient. We compare the ratio of the
projected or measured diffusion coefficient and the free intramembrane
diffusion coefficient, which is a parameter of the simulations, with analytical
results that rely on several approximations. We find that the simulations
always lead to a somewhat smaller diffusion coefficient than our analytical
approach. A detailed study of the correlations of the forces acting on the
particle indicates that the diffusing inclusion tries to follow favorable
positions on the membrane, such that forces along the trajectory are on average
smaller than they would be for random particle positions.Comment: 16 pages, 8 figure
Curvature correction to the mobility of fluid membrane inclusions
For the first time, using rigorous low-Reynolds-number hydrodynamic theory on curved surfaces via a Stokeslet-type approach, we provide a general and concise expression for the leading-order curvature correction to the canonical, planar, Saffman-DelbrĂŒck value of the diffusion constant for a small inclusion embedded in an arbitrarily (albeit weakly) curved fluid membrane. In order to demonstrate the efficacy and utility of this wholly general result, we apply our theory to the specific case of calculating the diffusion coefficient of a locally curvature inducing membrane inclusion. By including both the effects of inclusion and membrane elasticity, as well as their respective thermal shape fluctuations, excellent agreement is found with recently published experimental data on the surface tension dependent mobility of membrane bound inclusions
Fiskalische Kosten einer steuerlichen Förderung von Forschung und Entwicklung in Deutschland - Eine empirische Analyse verschiedener Gestaltungsoptionen
Der Beitrag berechnet die AufkommensausfĂ€lle verschiedener Gestaltungsmodelle fĂŒr eine steuerliche Forschungsförderung in Deutschland auf Basis eines Mikrosimulationsmodells. Die fiskalischen Kosten betragen zwischen 464 Mio. ⏠und 5.701 Mio. âŹ. Eine Erstattungsoption der Steuergutschrift ĂŒber die Gewerbe- und Körperschaftsteuerschuld hinaus ist unerlĂ€sslich, da sonst etwa ein Drittel der Unternehmen nicht oder nur teilweise in den Genuss der Förderung kommen wĂŒrde und sich dadurch starke Verzerrungen zwischen ertragsstarken und ertragsschwachen Unternehmen ergeben. Eine Differenzierung der FördersĂ€tze fĂŒr KMU und groĂe Unternehmen kann die AufkommensausfĂ€lle wirksam begrenzen. Eine Kappungsgrenze in Höhe eines absoluten Betrages ist wegen der Verzerrungen innerhalb der Gruppe groĂer Unternehmen ungĂŒnstig. Als besonders pragmatisch erscheint eine Verrechnung der Steuergutschrift mit der abzufĂŒhrenden Lohnsteuer
Model of SNARE-Mediated Membrane Adhesion Kinetics
SNARE proteins are conserved components of the core fusion machinery driving diverse membrane adhesion and fusion processes in the cell. In many cases micron-sized membranes adhere over large areas before fusion. Reconstituted in vitro assays have helped isolate SNARE mechanisms in small membrane adhesion-fusion and are emerging as powerful tools to study large membrane systems by use of giant unilamellar vesicles (GUVs). Here we model SNARE-mediated adhesion kinetics in SNARE-reconstituted GUV-GUV or GUV-supported bilayer experiments. Adhesion involves many SNAREs whose complexation pulls apposing membranes into contact. The contact region is a tightly bound rapidly expanding patch whose growth velocity increases with SNARE density . We find three patch expansion regimes: slow, intermediate, fast. Typical experiments belong to the fast regime where depends on SNARE diffusivities and complexation binding constant. The model predicts growth velocities s. The patch may provide a close contact region where SNAREs can trigger fusion. Extending the model to a simple description of fusion, a broad distribution of fusion times is predicted. Increasing SNARE density accelerates fusion by boosting the patch growth velocity, thereby providing more complexes to participate in fusion. This quantifies the notion of SNAREs as dual adhesion-fusion agents
CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers
The membrane attack complex (MAC) is one of the immune systemâs first responders. Complement proteins assemble on target membranes to form pores that lyse pathogens and impact tissue homeostasis of self-cells. How MAC disrupts the membrane barrier remains unclear. Here we use electron cryo-microscopy and flicker spectroscopy to show that MAC interacts with lipid bilayers in two distinct ways. Whereas C6 and C7 associate with the outer leaflet and reduce the energy for membrane bending, C8 and C9 traverse the bilayer increasing membrane rigidity. CryoEM reconstructions reveal plasticity of the MAC pore and demonstrate how C5b6 acts as a platform, directing assembly of a giant ÎČ-barrel whose structure is supported by a glycan scaffold. Our work provides a structural basis for understanding how ÎČ-pore forming proteins breach the membrane and reveals a mechanism for how MAC kills pathogens and regulates cell functions
Mechanical factors affecting the mobility of membrane proteins
To appear as a Chapter in "Physics of Biological Membranes", edited by Dr. Patricia Bassereau & Dr. Pierre Sens, Springer Nature SwitzerlandThe mobility of membrane proteins controls many biological functions. The application of the model of Saffman and Delbr\"uck to the diffusion of membrane proteins does not account for all the experimental measurements. These discrepancies have triggered a lot of studies on the role of the mechanical factors in the mobility. After a short review of the Saffman and Delbr\"uck model and of some key experiments, we explore the various ways to incorporate the effects of the different mechanical factors. Our approach focuses on the coupling of the protein to the membrane, which is the central element in the modelling. We present a general, polaron-like model, its recent application to the mobility of a curvature sensitive protein, and its various extensions to other couplings that may be relevant in future experiments
A multiscale analysis of diffusions on rapidly varying surfaces
Lateral diffusion of molecules on surfaces plays a very important role in various biological processes, including lipid transport across the cell membrane, synaptic transmission, and other phenomena such as exo- and endocytosis, signal transduction, chemotaxis, and cell growth. In many cases, the surfaces can possess spatial inhomogeneities and/or be rapidly changing shape. Using a generalization of the model for a thermally excited Helfrich elastic membrane, we consider the problem of lateral diffusion on quasi-planar surfaces, possessing both spatial and temporal fluctuations. Using results from homogenization theory, we show that, under the assumption of scale separation between the characteristic length and timescales of the membrane fluctuations and the characteristic scale of the diffusing particle, the lateral diffusion process can be well approximated by a Brownian motion on the plane with constant diffusion tensor D that depends on a highly nonlinear way on the detailed properties of the surface. The effective diffusion tensor will depend on the relative scales of the spatial and temporal fluctuations, and for different scaling regimes, we prove the existence of a macroscopic limit in each case
When Brownian diffusion is not Gaussian
It is commonly presumed that the random displacements that particles undergo as a result of the thermal jiggling of the environment follow a normal, or Gaussian, distribution. Here we reason, and support with experimental examples, that non-Gaussian diffusion in soft materials is more prevalent than expected.close442