Modified Epidermal Growth Factor Receptor (EGFR)-Bearing Liposomes (MRBLs) Are Sensitive to EGF in Solution

Cancers often overexpress EGF and other growth factors to promote cell replication and migration. Previous work has not produced targeted drug carriers sensitive to abnormal amounts of growth factors. This work demonstrates that liposomes bearing EGF receptors covalently crosslinked to p-toluic acid or methyl-PEO4-NHS ester (or, in short, MRBLs) exhibit an increased rate of release of encapsulated drug compounds when EGF is present in solution. Furthermore, the modified EGF receptors retain the abilities to form dimers in the presence of EGF and bind specifically to EGF. These results demonstrate that MRBLs are sensitive to EGF in solution and indicate that MRBL-reconstituted modified EGF receptors, in the presence of EGF in solution, form dimers which increase MRBL permeability to encapsulated compounds

Membrane-mediated interactions

Interactions mediated by the cell membrane between inclusions, such as membrane proteins or antimicrobial peptides, play important roles in their biological activity. They also constitute a fascinating challenge for physicists, since they test the boundaries of our understanding of self-assembled lipid membranes, which are remarkable examples of two-dimensional complex fluids. Inclusions can couple to various degrees of freedom of the membrane, resulting in different types of interactions. In this chapter, we review the membrane-mediated interactions that arise from direct constraints imposed by inclusions on the shape of the membrane. These effects are generic and do not depend on specific chemical interactions. Hence, they can be studied using coarse-grained soft matter descriptions. We deal with long-range membrane-mediated interactions due to the constraints imposed by inclusions on membrane curvature and on its fluctuations. We also discuss the shorter-range interactions that arise from the constraints on membrane thickness imposed by inclusions presenting a hydrophobic mismatch with the membrane.Comment: 38 pages, 10 figures, pre-submission version. In: Bassereau P., Sens P. (eds) Physics of Biological Membranes. Springer, Cha

Turbulence drives microscale patches of motile phytoplankton

Patchiness plays a fundamental role in phytoplankton ecology by dictating the rate at which individual cells encounter each other and their predators. The distribution of motile phytoplankton species is often considerably more patchy than that of non-motile species at submetre length scales, yet the mechanism generating this patchiness has remained unknown. Here we show that strong patchiness at small scales occurs when motile phytoplankton are exposed to turbulent flow. We demonstrate experimentally that Heterosigma akashiwo forms striking patches within individual vortices and prove with a mathematical model that this patchiness results from the coupling between motility and shear. When implemented within a direct numerical simulation of turbulence, the model reveals that cell motility can prevail over turbulent dispersion to create strong fractal patchiness, where local phytoplankton concentrations are increased more than 10-fold. This "unmixing" mechanism likely enhances ecological interactions in the plankton and offers mechanistic insights into how turbulence intensity impacts ecosystem productivity

Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites

C-reactive protein (CRP) concentrations rise in response to tissue injury or infection. Circulating pentameric CRP (pCRP) localizes to damaged tissue where it leads to complement activation and further tissue damage. In-depth knowledge of the pCRP activation mechanism is essential to develop therapeutic strategies to minimize tissue injury. Here we demonstrate that pCRP by binding to cell-derived microvesicles undergoes a structural change without disrupting the pentameric symmetry (pCRP*). pCRP* constitutes the major CRP species in human-inflamed tissue and allows binding of complement factor 1q (C1q) and activation of the classical complement pathway. pCRP*–microvesicle complexes lead to enhanced recruitment of leukocytes to inflamed tissue. A small-molecule inhibitor of pCRP (1,6-bis(phosphocholine)-hexane), which blocks the pCRP–microvesicle interactions, abrogates these proinflammatory effects. Reducing inflammation-mediated tissue injury by therapeutic inhibition might improve the outcome of myocardial infarction, stroke and other inflammatory conditions