Lipid membrane-mediated attraction between curvature inducing objects

The interplay of membrane proteins is vital for many biological processes, such as cellular transport, cell division, and signal transduction between nerve cells. Theoretical considerations have led to the idea that the membrane itself mediates protein self-organization in these processes through minimization of membrane curvature energy. Here, we present a combined experimental and numerical study in which we quantify these interactions directly for the first time. In our experimental model system we control the deformation of a lipid membrane by adhering colloidal particles. Using confocal microscopy, we establish that these membrane deformations cause an attractive interaction force leading to reversible binding. The attraction extends over 2.5 times the particle diameter and has a strength of three times the thermal energy (−3.3 kBT). Coarse-grained Monte-Carlo simulations of the system are in excellent agreement with the experimental results and prove that the measured interaction is independent of length scale. Our combined experimental and numerical results reveal membrane curvature as a common physical origin for interactions between any membrane-deforming objects, from nanometre-sized proteins to micrometre-sized particles

Localized energy for wave equations with degenerate trapping

Localized energy estimates have become a fundamental tool when studying wave equations in the presence of asymptotically at background geometry. Trapped rays necessitate a loss when compared to the estimate on Minkowski space. A loss of regularity is a common way to incorporate such. When trapping is sufficiently weak, a logarithmic loss of regularity suffices. Here, by studying a warped product manifold introduced by Christianson and Wunsch, we encounter the first explicit example of a situation where an estimate with an algebraic loss of regularity exists and this loss is sharp. Due to the global-in-time nature of the estimate for the wave equation, the situation is more complicated than for the Schr\"{o}dinger equation. An initial estimate with sub-optimal loss is first obtained, where extra care is required due to the low frequency contributions. An improved estimate is then established using energy functionals that are inspired by WKB analysis. Finally, it is shown that the loss cannot be improved by any power by saturating the estimate with a quasimode.Comment: 18 page

Increased expression of matrix metalloproteinase 3 can be attenuated by inhibition of microRNA-155 in cultured human astrocytes

Background: Temporal lobe epilepsy (TLE) is a chronic neurological disease, in which about 30% of patients cannot be treated adequately with anti-epileptic drugs. Brain inflammation and remodeling of the extracellular matrix (ECM) seem to play a major role in TLE. Matrix metalloproteinases (MMPs) are proteolytic enzymes largely responsible for the remodeling of the ECM. The inhibition of MMPs has been suggested as a novel therapy for epilepsy; however, available MMP inhibitors lack specificity and cause serious side effects. We studied whether MMPs could be modulated via microRNAs (miRNAs). Several miRNAs mediate inflammatory responses in the brain, which are known to control MMP expression. The aim of this study was to investigate whether an increased expression of MMPs after interleukin-1β (IL-1β) stimulation can be attenuated by inhibition of the inflammation-associated miR-155.Methods: We investigated the expression of MMP2, MMP3, MMP9, and MMP14 in cultured human fetal astrocytes after stimulation with the pro-inflammatory cytokine IL-1β. The cells were transfected with miR-155 antagomiR, and the effect on MMP3 expression was investigated using real-time quantitative PCR and Western blotting. Furthermore, we characterized MMP3 and miR-155 expression in brain tissue of TLE patients with hippocampal sclerosis (TLE-HS) and during epileptogenesis in a rat TLE model.Results: Inhibition of miR-155 by the antagomiR attenuated MMP3 overexpression after IL-1β stimulation in astrocytes. Increased expression of MMP3 and miR-155 was also evident in the hippocampus of TLE-HS patients and throughout epileptogenesis in the rat TLE model.Conclusions: Our experiments showed that MMP3 is dynamically regulated by seizures as shown by increased expression in TLE tissue and during different phases of epileptogenesis in the rat TLE model. MMP3 can be induced by the pro-inflammatory cytokine IL-1β and is regulated by miR-155, suggesting a possible strategy to prevent epilepsy via reduction of inflammation

Lipid membrane-mediated attraction between curvature inducing objects

Biological and Soft Matter Physic