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In biological systems, charged membrane surfaces are surrounded by charged molecules such as electrolyte ions and proteins. Our recent experiments in the systems of giant phospholipid vesicles indicated that some of the blood plasma proteins (macro-ions) may promote adhesion between equally charged membrane surfaces. In this work, theory was put forward to describe an IgG antibody-mediated attractive interaction between negatively charged membrane surfaces which was observed in experiments on giant phospholipid vesicles with cardiolipin-containing membranes. The attractive interactions between negatively charged membrane surfaces in the presence of negatively and positively charged spherical macro-ions are explained using functional density theory and Monte Carlo simulations. Both, the rigorous solution of the variational problem within the functional density theory and the Monte Carlo simulations show that spatial and orientational ordering of macro-ions may give rise to an attractive interaction between negatively charged membrane surfaces. It is also shown that the distinctive spatial distribution of the charge within the macro-ions (proteins) is essential in this process.

The temperature-induced budding of POPC-cardiolipin-cholesterol, POPC-POPS-cholesterol and POPC-POPG-cholesterol giant lipid vesicles in the presence of beta 2-glycoprotein I (beta 2-GPI) in the outer solution was studied experimentally and theoretically. The observed budding transition of vesicles was continuous which can be explained by taking into account the orientational ordering and direct interactions between oriented lipids. The attachment of positively charged beta 2-GPI to the negatively charged outer surface of POPC-cardiolipin-cholesterol, POPC-POPS-cholesterol and POPC-POPG-cholesterol giant vesicles caused coalescence of the spheroidal membrane bud with the parent vesicle before the bud could detach from the parent vesicle, i.e. vesiculate. Theoretically, the protein-mediated attraction between the membrane of a bud and the parent membrane was described as an interaction between two electric double layers. It was shown that the specific spatial distribution of charge within beta 2-GPI molecules attached to the negatively charged membrane surface may explain the observed attraction between like-charged membrane surfaces.

Abstract:Microvesicles which are pinched off the cell membrane can be considered extracellular organelles which mediate interaction between distal cells. They were suggested to play an important role in many diseases including autoimmune disorders, however, standard methods for their assessment have not yet been decided upon while their clinical relevance and the underlying mechanisms are yet unclear. We present a pilot study results involving atomic force microscope (AFM) and scanning electron microscope (SEM) images of the material isolated from peripheral blood of healthy donors and from synovial fluid of patients with psoriatic arthritis and rheumatoid arthritis, which is expected to contain microvesicles. Micrographs reveal in the samples isolated from blood the presence of globular and tubular structures which are most probably microvesicles while the identity of grain-like structures isolated from synovial fluid remains obscure. To the best of our knowledge the AFM and SEM images of the material isolated from synovial fluid are presented for the first time.