Projects / Programmes
Mediated interactions between membranous structures
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B120 |
Biomedical sciences |
Molecular biophysics |
Microparticles; Nanorafts; Polivalent Ions; Vesicles; Membranes; Coagulation;
Researchers (18)
Organisations (2)
Abstract
Function of cell membranes is an interactive process. One of the mechanisms for exchange of substances and information between cells is based on microvesicles that are formed by budding of the basic membrane, enter into blood circulation and interact with the membrane of a distant cell. An important part of this process is the surrounding solution – the blood serum. Membrane budding, fission of microvesicles from the membrane and coalescence of membranes is affected by molecules and clusters of molecules in the blood serum such as proteins of immune system (antigens and antibodies), microparticles containing lipid molecules and various exogenously added substances. Giant phospholipid vesicles with controlled composition and controlled environment represent an appropriate model to study mediated interactions between cell membranes. In order to analyze the communication mechanisms of cell membranes and blood coagulation mechanisms in particular, we propose to study in the present project the influence of microvesicles, microparticles, various antibodies, serum proteins and active substances with pro- or anticoagulant activity in vivo on the properties of giant phospholipid vesicles and collective interactions between them. We shall also theoretically describe membrane budding and coalescence by using models based on the microscopic description of membrane constituents and methods of statistical mechanics. Expected results will contribute to better understanding of interactions between membranes, microparticles, microvesicles and added active substances – interactions that play an important part in the formation of blood clots.
Significance for science
Results of this project contribute to the development of the field of membrane biophysics, theory of the electric double layer and to medical science.
In the field of membrane biophysics we have developed two theories which are important for the process of microvesiculation: a theory which describes the curvature-dependent lateral and orientational distribution of membrane constituents, and a theory which describes the mediated attractive interaction between membranes. Both theories are based on the same principle: orientational ordering of the system constituents which lowers the free energy of the system. Orientational ordering stabilizes the shape and the distribution, and also explains the attraction between the like-charged membranes. The theory which decribes lateral and orientational ordering of membrame constituents provided explanation for the stability of thin necks connecting the bud and the mother membrane, membrane nanotubes and the inverted hexahonal lipid phase.
In describing the mediated attractive interaction between membranes we have introduced a rigorous consideration of the microscopic charge denstiy, which is a novelty in the theory of the electric double layer of extended charges.
In the field of medical science we have established an in vitro experimental system based on phospholipid vesicles which could be used to assess the ability of the solution to mediate attractive interaction between membranes. We have introduced a method for quantitative assessment of the interaction between membranes, by an average contact angle between the adhered vesicles. The method was used to study the effect of antiphospholipid antibodies, beta 2 glycoprotein I and plasmas of different subjects.
Significance for the country
Experiments with giant phospholipid vesicles have shown a possible important effect of plasma proteins in mediating attractive interaction between membranes. Based on experiments with antiphospholipid antibodies and the cofactor for their binding to phospholipids (beta 2 glycoprotein I) we have proposed a hypothesis on anticoagulant effect of plasma proteins. By mediating attractive interaction between membranes, plasma proteins cause adhesion of the bud to the mother membrane and thereby prevent pinching off procoagulant microvesicles from the mother membrane. Validation of this hypothesis, as indicated in two publications within this project, would mean an important step forward in understanding processes involved in blood clot formation. Therefore, results of the project indicate a possibility of the imporovement of the method for assessment of the risk for thromboembolic events (such as stroke, lung emboly and miocardial infarction). Since these are common diseases with important consequences for the quality of life and social and economic consequences, continuation of the research could have an important favorable effect on the sevelopment of Slovenia.
Most important scientific results
Annual report
2008,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
final report,
complete report on dLib.si
