What We Do
We try to decipher how biological systems work from nanoscale to macroscale by employing a combination of computer simulations and experiments. We investigate models of biosystems at the level of molecules by applying modern computational tools. More specifically, we perform computer simulations of time-dependent behavior of small fragments of biological systems consisting of hundreds of thousands of individual chemical molecules. Such simulations act as 'computational supermicroscope' that enables us to look at biosystems at the nanometer length-scale and up to microsecond time-scale. On the experimental side, we build minimalistic wet-lab models of biological systems and study them by various experimental techniques. These in vitro bio-mimics allow us to assess macro-scale properties of the investigated systems under well-controlled conditions. We then combine the two approaches to find out what is a molecular-level basis of the observed macroscopic phenomena.
Why We Do It
Our goal is to understand biological systems in detail. This can be achieved only by knowing how the underlying molecular nature of these systems determines their structure and function. The primary goal is not merely to understand nature but to further use this knowledge, for instance, for a design of biomimicking artificial constructs, drug design, or nanotechnological applications.
What Systems We Investigate
We study several classes of biological systems. Our main focus is on lipid- and protein-containing models.
- First, we study lipid bilayers. Such bilayers are main constituents of cellular membranes, for instance, the plasma membrane that encloses each living cell and acts as a complex, partially permeable barrier between the cell and its environment. learn more...
- Second, we are interested in the thin layer of lipids that covers the ocular surface of the human eye, so-called Tear Film Lipid Layer. Its main function is a reduction of the surface tension of the tear film/air interface. learn more...
- Third, we look at lipid mono- and multilayers at water/air boundary. We are mainly interested in lipid monolayers in the context of the lung surfactant. //learn more...
- Fourth, we look at how short transmembrane peptides behave in cell membranes. Some of the membrane proteins that span across cell membrane have relatively simple transmembrane domains that are able to modulate protein's behavior. //learn more...
What Methods We Use
We perform computer simulations, mainly classical molecular dynamics (MD). Specialized, highly parallelized software is used, and computations are performed at supercomputers in computational centers or locally at modern computer clusters. Regarding software, we mostly use the GROMACS code (>>). We also employ quantum chemical calculations both for force field parameterization and for combined quantum-classical simulations. We do a lot of coding/scripting, mainly with Python (>>). For visualization, we primarily employ the VMD code (>>).
In our experimental work, we build simple mimics of the investigated biological systems (for instance, lipid films that model Tear Film Lipid Layer). Here, we try to mimic the investigated systems not only by basic replication of their composition but also by reproducing such essential characteristics as system geometry, dynamics, or interactions with environment. In practice, we realize this by combining mesofluidic approaches with microscopic techniques.
We are looking for talented people, mainly PhD and master students, to join our lab.
Lipid bilayers are main constituents of cell membranes which enclose each living cell and act as complex, dynamic, partially permeable barriers between the cell and its environment. Each living cell transfers various material in and out across its cellular membrane. Moreover, bacteria and viruses always encounter the membrane when attacking a cell. Similarly, if we want to transport a drug molecule into a cell, we must find a way to transfer it across the membrane. These three examples demonstrate why it is crucial to gain a molecular-level understanding of lipid membranes.
Tear Film Lipid Layer
Tear Film Lipid Layer is a thin layer of lipids that covers the ocular surface of the human eye. Its main function is a reduction of the surface tension of the tear film/air interface. Moreover, the presence of the TFLL prevents rapid evaporation of water from the underlying water aqueous phase. TFLL deficiencies lead to evaporative dry eye syndrome, one of the commonly reported eye ailments. Despite its vital role for eye function, the structure and other properties of TFLL at the molecular level are essentially unknown and only recently studied. We recently constructed a computational model of the TFLL and currently we employ it to investigate the structure and dynamics of the TFLL.
Lipid Mono- and Multilayers
Lipid mono- and multilayers at water/air boundary are interesting preliminarily in the context of the lung surfactant. The gas exchange in lungs occurs through a layer of lipids that covers the surface of lung alveoli cells. This lipid layer is the first line of defense between air and the organism and is prone to damage by such environmental factors as free radicals and air pollutants. On the other hand, this barrier is relatively easy to cross and may serve as a convenient drug delivery pathway. This is why we try to understand lipid monolayers at the level of individual molecules better.
Some of the membrane proteins that span across cell membrane have a relatively simple transmembrane domain that still can control protein's behavior. Moreover, this domain is directly interacting with membrane lipids; hence it influences membrane properties. Similarly, the lipid-protein interactions modulate protein behavior. These issues cannot be understood without knowledge about lipid-protein interactions at the level of individual chemical moieties.