Projects / Programmes
Experimental biophysics of complex systems
January 1, 2009
- December 31, 2014
| Code |
Science |
Field |
Subfield |
| 1.02.00 |
Natural sciences and mathematics |
Physics |
|
| Code |
Science |
Field |
| B260 |
Biomedical sciences |
Hydrobiology, marine biology, aquatic ecology, limnology |
| Code |
Science |
Field |
| 1.03 |
Natural Sciences |
Physical sciences |
Biophysics, membranes, cells, tissues, magnetic resonance, spin labels, spin traps, antioxydative processes, spectral simulation, liposomes, nanoparticles, oxymetry, diffusion, spin echo, porous heterogeneous structures, flow, chromatography, agro technology, catalyze
Researchers (26)
Organisations (2)
Abstract
Based on numerous experiences in various experimental techniques and approaches of electron paramagnetic resonance spectroscopy-EPR (like spin labelling-SL EPR, concentration imaging-CI EPR, kinetic imaging-cI EPR and one-dimensional imaging-1D EPR) as well as expert knowledge in development of the tools for simulation of complex biosystem, characterization like biomembranes and membrane proteins we will continue the research on:
-glycosylated cell surfaces, their rheology, dynamics and function based on spin labelling of the cell surfaces, simulation of the aggregation of sugar oligomers and SAXS measurements (small angle X-ray scattering),
-the signal transduction pathways and different interaction schemes between the constituents of biomembranes like enzymes, pumps, receptors, membrane domains and rafts, glycocalyx, etc.; based on those findings the possibilities to apply of lipid model systems in the development of lipid-based biosensors will be explored,
-the functional properties of particular membrane proteins with site-directed spin labelling and exploration of their conformational freedom as well as low-resolution structure based on SDSL EPR and GHOST condensation results,
-the effects of bioactive substances (chemotherapeutics, toxins, anaesthetics, etc.) on the lateral structure and function of membrane domains and the antioxydative properties of model cells and cells from different cell lines, with special focus on nonlinear phenomena in biosystems
-the structure of the solid lipid nanoparticles for targeted drug delivery to tissues with special emphasis on understanding of the mechanisms of transport, partitioning and interaction of the nanostructures with cells (fusion, endocythosis, adsorption)
-the reactive free radicals and protection against them with methods based on spin traps
-the effect of oxygenation of cells and tissues in various pathological processes in vivo as well as the effect of various therapies (radiotherapy, chemotherapy, electrotherapy and their combinations) will be explored with the method of EPR oxymetry
In the second part of our research with magnetic resonance we will explore biological processes in vivo and in vitro. It is the spectroscopy using hydrogen and phosphorous nuclei.
-Processes of dissolution of blood cloths,where the dynamical MR imaging was used to describe the efficiency of different drugs and approaches that help to dissolve the blood cloths in an artificial blood circulation system. Such research leads to improvement of healing treatments at conditions of infarction.
-The use of MR in dentistry will show that MR microscopy provides more detailed images of the dental pulp, as the presently applied X-ray images. This is especially important and helpful in ortodontic treatments in dentistry.
-The growth of tree and the reparation of damage is related with the distribution of water in the damaged tissue. Here MR microscopy provides highly selective images showing the distribution of water in the wood.
-Exploration of porous material with MR to describe the diffusion process of molecules. These processes are drastically different as compared with non-hindered liquids, since here the active space available is the system of channels determined by the porous medium. The dynamics of molecular movements must include the collisions with the walls of channels that can be only understood with modern methods to measure the diffusion. MRI belongs to the most promising methods to explore grainy materials, especially to follow the mobility of the grain particles.
-MRI is a nondestructive method to take images in a randomly chosen cross-section of the sample and the measurement of the speed of the motion of these particles. Between the important problems where MRI can be efficient: study of the convective flows, imaging of distribution of the mechanical stresses before the onset of gliding of the grain particles.
Significance for science
Our research group studied various problems of biophysics in different scales. Thus, at the molecular level we have developed a new method based on SDSL EPR and simulations of local conformational spaces. The method represents an alternative to the existing methods of high-resolution structural characterization of proteins and their complexes. Existing methods give under physiological conditions and with fast dynamic phenomena poor results. With the development of the combined SL EPR – FMS method, we introduced a completely new approach to the study of the structural properties and the role of membrane domains. The approach is important in studies of membrane biophysics, this is a problem of lateral structure or the occurrence of membrane domains and their role in intercellular interactions and interactions with bioactive substances. Over the last decade generally accepted belief that the active membrane processes determine the main characteristics of membrane proteins is changing due to new findings of research. Nevertheless, the lateral heterogeneity of the membranes remained unresolved because of conflicting results of spectroscopic and microscopic techniques, most of which originate from high experimental requirements for the sensitivity and resolution in the nanometer and nanosecond scale. At a larger scale, we development new MRI techniques, such as fast (single-shot) MR imaging, diffusion-weighted MR imaging and the methods of MR imaging in a weak field. With the methods we were able to get a non-destructive and efficient insight into various dynamic phenomena and structure on the micrometer scale in biological systems in vivo. With the new methods, we can explain the mechanisms of formation and decay of cell clusters, for example, the dissolution of blood clots. New MRI methods have particular importance for monitoring the dosage and targeting transport of active substances in living organisms. The development of methods of MR imaging in a weak magnetic field opened new research opportunities, as in a weak magnetic field relaxation dynamics is different than in a higher field, thereby allowing complementary measurements of spectra and inter-spin interactions. Discoveries achieved by the group are also of a great importance in understanding the mechanisms of various pathological phenomena in their treatment. Our research in the field of antimicrobial properties of nanomaterials lead us to important discoveries on the interactions between cells and nanomaterials. These findings are important for understanding the safety of new nanotechnologies and the use of nanoparticles. We can highlight the outstanding interdisciplinary orientation of our research. The research is connecting different areas of natural sciences, biotechnology and medicine. In these problems physics enabled insights into mechanisms of structure, self-organization and dynamics of complex biological systems.
Significance for the country
Research on membranes, tissues and organisms led us to understanding of the mechanisms of interactions in biological systems and to understanding of pathophysiological conditions, such as cancer and vascular diseases. Development of antiviral medicines has been enabled with the new insights into the structural biophysics of protein complexes. New research in membrane biophysics and new oximetry methods improved the understanding and treatment of cancer. We also developed new efficient methods of monitoring delivery systems for drugs, which is important for the pharmaceutical industry. Knowledge on the interactions in membranes enabled us to develop biosensors for monitoring levels of pesticides in food and environmental samples. Understanding the interactions between cells and nanoparticles enabled us development of safe industrial self-cleaning surfaces. In this area, we also cooperated with domestic industry (Gorenje, VINPROM). With the development of new methods of magnetic resonance imaging, we contributed to the development of medical diagnostics and in vivo and to training of medical personnel performing clinical MRI. In this way we also contributed to a better quality of health services. We used some of new MRI methods to monitor the treatment of blood clots and pulmonary embolism as well as for following the active substances in the different treatments. We offered our knowledge in this field to pharmaceutical company Krka with which we collaborate since 2010 in the development of new drugs. We were also using MRI to monitor treatment of food by heat and ongoing processes during food storage. The group's work was also important in the field of education. Thus, several new science doctors and master degree students finished their education in our research laboratories studying research problems of the group. Some of them got important positions in R & D industry. Special attention was also devoted to improving education and popularization of science. With new approaches in the teaching process, we encourage innovation in the secondary school and university level.
Most important scientific results
Annual report
2009,
2010,
2011,
2012,
2013,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
2012,
2013,
final report,
complete report on dLib.si
