In this talk I discuss the general question of the portability of Molecular Dynamics codes for diffusive systems on parallel computers of the APE family. The intrinsic single precision arithmetics of the today available APE platforms does not seem to affect the numerical accuracy of the simulations, while the absence of integer addressing from CPU to individual nodes puts strong constraints on the possible programming strategies. Liquids can be very satisfactorily simulated using the "systolic" method. For more complex systems, like the biological ones at which we are ultimately interested in, the "domain decomposition" approach is best suited to beat the quadratic growth of the inter-molecular computational time with the number of elementary components of the system. The promising perspectives of using this strategy for extensive simulations of lipid bilayers are briefly reviewed.
In this work we to develop a general statistical mechanic formalism to study systems restricted to surfaces of revolution, these are a very well model to study the termodinamical properties of microbiological systems and macromolecules lies on biological membranes such as cellular well.
Ice formation in model biological membranes is studied by SAXS and WAXS in the presence of cryoprotectors: dimethyl sulfoxide and glycerol. Three types of phospholipid membranes: DPPC, DMPC, DSPC are chosen for the investigation as well-studied model biological membranes. A special cryostat is used for sample cooling from 14.1C to -55.4C. The ice formation is only detected by WAXS in binary phospholipid/water and ternary phospholipid/cryoprotector/water systems in the condition of excess solvent. Ice formation in a binary phospholipid/water system creates an abrupt decrease of the membrane rep…
The small-angle X-ray and neutron scattering, time resolved X-ray small-angle and wide-angle diffraction coupled with differential scanning calorimetry have been applied to the investigation of unilamellar and multilamellar dimyristoylphosphatidylcholine (DMPC) vesicles in sucrose buffers with sucrose concentrations from 0 to 60%. Sucrose buffer decreased vesicle size and polydispersity and increased an X-ray contrast between phospholipid membrane and bulk solvent sufficiently. No influence of sucrose on the membrane thickness or mutual packing of hydrocarbon chains has been detected. The regi…
Biological membranes mainly consist of lipids and proteins. While the proteins have many functions as single molecules, the membrane as a whole displays physical properties that cannot be explained on the single molecule level. For example, membranes show melting events, phase behavior, and elasticity. Biomembranes adapt their composition such that the physical properties are maintained when the external conditions change. This gives a role to changes in composition, to temperature and pressure. This article introduces into the physics of membranes as a whole and shows how phenomena as permeab…
We discuss the role coarse-grained models play in the investigation of the structure and thermodynamics of bilayer membranes, and we place them in the context of alternative approaches. Because they reduce the degrees of freedom and employ simple and soft effective potentials, coarse-grained models can provide rather direct insight into collective phenomena in membranes on large time and length scales. We present a summary of recent progress in this rapidly evolving field, and pay special attention to model development and computational techniques. Applications of coarse-grained models to chan…
Biological cell suspensions are known to show dielectric dispersions due to the Maxwell-Wagner mechanism. Many examples are summarized in a number of papers by Schwan [7, 9, 10]. By the application of an appropriate analysis to the dielectric dispersion, it is possible to estimate electrical phase parameters related to protoplasm and cell membrane. A dielectric theory of interfacial polarization for a suspension of conducting particles (protoplasm) covered with poorly conducting shells (plasma membrane) was developed by Pauly and Schwan [7], and was satisfactory applied for low volume fraction…
Membrane tubulation is a ubiquitous process that occurs both at the plasma membrane and on the membranes of intracellular organelles. These tubulation events are known to be mediated by forces applied on the membrane either due to motor proteins, by polymerization of the cytoskeleton, or due to the interactions between membrane proteins binding onto the membrane. The numerous experimental observations of tube formation have been amply supported by mathematical modeling of the associated membrane mechanics and have provided insights into the force-displacement relationships of membrane tubes. R…
Lipid rafts are heterogeneous dynamic lipid domains of the cell membranes that are involved in several biological processes, like protein and lipids specific transport and signaling. Our understanding of lipid raft formation is still limited, due to the transient and elusive nature of these domains {\it in vivo}, in contrast to the stable phase-separated domains observed in artificial membranes. Inspired by experimental findings highlighting the relevance of transmembrane proteins for lipid rafts, we investigate lipid domain nucleation by coarse-grained molecular dynamics and Ising model simul…
Lipid bilayers forming biological membranes are known to behave as viscous 2D fluids on submicrometer scales; usually they contain a large number of active protein inclusions. Recently, it has been shown [Proc. Nat. Acad. Sci. USA 112, E3639 (2015)] that such active proteins should in- duce non-thermal fluctuating lipid flows leading to diffusion enhancement and chemotaxis-like drift for passive inclusions in biomembranes. Here, a detailed analytical and numerical investigation of such effects is performed. The attention is focused on the situations when proteins are concentrated within lipid …
The behaviour of a system of ion channels formed across the cell membrane is presented. The infinite number of channels with an infinite coupling is introduced first as a reference point for the detailed derivation of the thermal-equilibrium probability distribution and the classification of the phase transitions. Fluctuations in a finite system are discussed next. We propose a new, step-like model of the ion channel switching, for which we provide the analytical results. The relation of this model to experiment is also provided. Finally, the master equation for the finite channel-number membr…
Native membranes of biological cells display melting transitions of their lipids at a temperature of 10-20 degrees below body temperature. Such transitions can be observed in various bacterial cells, in nerves, in cancer cells, but also in lung surfactant. It seems as if the presence of transitions slightly below physiological temperature is a generic property of most cells. They are important because they influence many physical properties of the membranes. At the transition temperature, membranes display a larger permeability that is accompanied by ion-channel-like phenomena even in the comp…
When considering flows in biological membranes, they are usually treated as flat, though more often than not, they are curved surfaces, even extremely curved, as in the case of the endoplasmic reticulum. Here, we study the topological effects of curvature on flows in membranes. Focusing on a system of many point vortical defects, we are able to cast the viscous dynamics of the defects in terms of a geometric Hamiltonian. In contrast to the planar situation, the flows generate additional defects of positive index. For the simpler situation of two vortices, we analytically predict the location o…
The plasma membrane of living cells is compartmentalized at multiple spatial scales ranging from the nano- to the meso-scale. This non-random organization is crucial for a large number of cellular functions. At the nanoscale, cell membranes organize into dynamic nano-assemblies enriched by cholesterol, sphingolipids and certain types of proteins. Investigating these nano-assemblies known as lipid rafts is of paramount interest in fundamental cell biology. However, this goal requires simultaneous nanometer spatial precision and microsecond temporal resolution which is beyond the reach of common…
Nanoscale membrane assemblies of sphingolipids, cholesterol, and certain proteins, also known as lipid rafts, play a crucial role in facilitating a broad range of important cell functions. Whereas on living cell membranes lipid rafts have been postulated to have nanoscopic dimensions and to be highly transient, the existence of a similar type of dynamic nanodomains in multicomponent lipid bilayers has been questioned. Here, we perform fluorescence correlation spectroscopy on planar plasmonic antenna arrays with different nanogap sizes to assess the dynamic nanoscale organization of mimetic bio…
While modern structural biology has provided us with a rich and diverse picture of membrane proteins, the biological function of membrane proteins is often influenced by the mechanical properties of the surrounding lipid bilayer. Here we explore the relation between the shape of membrane proteins and the cooperative function of membrane proteins induced by membrane-mediated elastic interactions. For the experimental model system of mechanosensitive ion channels we find that the sign and strength of elastic interactions depend on the protein shape, yielding distinct cooperative gating curves fo…
The electropermeabilization of biological cell membranes by the application of an external field occurs whenever an applied field exceeds a threshold value. For fields above this threshold value but less than another critical value, the pores formed in the membrane are transient or reversible. Several mechanisms have been proposed for the formation of these transient pores. Here we examine the local electric fields generated for the configuration of cells embedded in a polycarbonate filter, both in the region in and around the pore. We consider the shear forces created in the membrane due to t…
High-resolution structural information on membrane proteins is essential for understanding cell biology and for structure-based design of new medical drugs and drug delivery strategies. X-ray diffraction (XRD) can provide Ångstrom-level information about the structure of membrane proteins. Ideally protein structures should be solved in environments as close to the original biological context as possible. However, it is virtually impossible to crystallize proteins within the complex environment of a biological membrane. Instead, membrane proteins are typically transferred from their native memb…
Animal cells are both encapsulated and subdivided by lipid bilayer membranes. Beyond just acting as boundaries, these membranes' shapes influence the function of cells and their compartments. Physically, membranes are two-dimensional fluids with complex elastic behavior, which makes it impossible, for all but a few simple cases, to predict membrane shapes analytically. Instead, the shape and behavior of biological membranes can be determined by simulations. However, the setup and use of such simulations require a significant programming background. The availability of open-source and user-frie…
Technical challenges in molecule sensing and chemical detection have created an increasing demand for transformative materials with high sensitivity and specificity. Biohybrid nanopores have attracted growing interest as they can ideally combine the durability of solid-state nanopores with the precise structure of biological nanopores. Particular care must be taken to control how biological nanopores adapt to their surroundings once in contact with the solid-state nanopore. Two major challenges are to precisely control this adaptability under dynamic conditions and provide predesigned function…
Although promising for biomedicine, the clinical translation of inorganic nanoparticles (NPs) is limited by low biocompatibility and stability in biological fluids. A common strategy to circumvent this drawback consists in disguising the active inorganic core with a lipid bilayer coating, reminiscent of the structure of the cell membrane to redefine the chemical and biological identity of NPs. While recent reports introduced membrane coating procedures for NPs, a robust and accessible method to quantify the integrity of the bilayer coverage is not yet available. To fill this gap, we prepared S…
A qualitative model is presented, suggesting gravitational information is transduced into biological systems primarily by its effect on spatially organised membrane and cytoplasmic flows. Continuous low affinity interactions between membrane bound cytoskeletal proteins and phospholipid flows that are undergoing forced convective and shear driven flows are shown to convert this information into spatial protein patterns, and hence cell shape. As applied here to plant cells, the feedback mechanism is shown capable not only of establishing the strict nanometer scale parallelism that exists between…
Most biological molecules contain acido-basic groups that modulate their structure and interactions. A consequence is that pH gradients, local heterogeneities and dynamic variations are used by cells and organisms to drive or regulate specific biological functions including energetic metabolism, vesicular traffic, migration and spatial patterning of tissues in development. While the direct or regulatory role of pH in protein function is well documented, the role of hydrogen and hydroxyl ions in modulating the properties of lipid assemblies such as bilayer membranes is only beginning to be unde…
Pure FENE Bond Potential for Soft Matter and Biological Simulations: Theory, HOOMD-blue Implementation, and Applications to Polymer, Colloidal, and Membrane Systems
Electroporation of biological cell membranes is a phenomena that occurs almost universally at a transmembrane potential of approximately 1000 mV. Theories of pore formation have been proposed based on electrocompression (Crowley 1972, Malderelli and Steebe 1992), local membrane defects (Abidor and Chizdhmazdev 1979, Weaver and Mintzer 1981, Sugar 1981), and Statistical models were proposed by (Sowers and Lieber 1986). However, these theories do not in general derive the form of the electric field within the pore. In this paper, we present a view that is useful in describing the biological memb…
The biological membrane, which compartmentalizes the cell and its organelles, exhibit wide variety of macroscopic shapes of varying morphology and topology. A systematic understanding of the relation of membrane shapes to composition, external field, environmental conditions etc. have important biological relevance. Here we review the triangulated surface model, used in the macroscopic simulation of membranes and the associated Monte Carlo (DTMC) methods. New techniques to calculate surface quantifiers, that will facilitate the study of additional in-plane orientational degrees of freedom, has…
Photothermal therapies are based on the optical excitation of plasmonic nanoparticles in the biological environment. The effects of the irradiation on the biological medium depend critically on the heat transfer process at the nanoparticle interface, on the temperature reached by the tissues as well as on the spatial extent of temperature gradients. Unfortunately, both the temperature and its biological effects are difficult to be probed experimentally at the molecular scale. Here, we approach this problem using nonequilibrium molecular dynamics simulations. We focus on photoporation, a photot…
Biological signaling is imagined as a combination of activation and transport. The former is triggered by local molecular interactions and the latter is the result of molecular diffusion. However, other fundamental physical principles of communication have yet to be addressed. We have recently shown, that lipid interfaces allow for the excitation and propagation of sound pulses. Here we demonstrate, that these reversible perturbations can control the activity of membrane embedded enzymes without the necessity of molecular transport. They therefore allow for the rapid communication between dist…
Currently, biological signaling is envisaged as a combination of activation and movement, triggered by local molecular interactions and molecular diffusion, respectively. However, we here suggest, that other fundamental physical mechanisms might play an at least equally important role. We have recently shown that lipid interfaces permit the excitation and propagation of sound pulses. Here we demonstrate that these reversible perturbations can control the activity of membrane-embedded enzymes without a requirement for molecular transport. They can thus facilitate rapid communication between dis…
Membrane based nanocalorimeters have been developed for ac calorimetry experiments. It has allowed highly sensitive measurements of heat capacity from solid state physics to complex systems like polymers and proteins. In this article we review what has been developed in ac calorimetry toward the measurement of very small systems. Firstly, at low temperature ac calorimetry using silicon membrane permits the measurement of superconducting sample having geometry down to the nanometer scale. New phase transitions have been found in these nanosystems illustrated by heat capacity jumps versus the ap…
The equations governing lipid membrane dynamics in planar, spherical, and cylindrical geometries are presented here. Unperturbed and first-order perturbed equations are determined and non-dimensionalized. In membrane systems with a nonzero base flow, perturbed in-plane and out-of-plane quantities are found to vary over different length scales. A new dimensionless number, named the Scriven--Love number, and the well-known Föppl--von Kármán number result from a scaling analysis. The Scriven--Love number compares out-of-plane forces arising from the in-plane, intramembrane viscous stresses to the…
The understanding of dynamics and functioning of biological membranes and in particular of membrane embedded proteins is one of the most fundamental problems and challenges in modern biology and biophysics. In particular the impact of membrane composition and properties and of structure and dynamics of the surrounding hydration water on protein function is an upcoming hot topic, which can be addressed by modern experimental and computational techniques. Correlated molecular motions might play a crucial role for the understanding of, for instance, transport processes and elastic properties, and…
Microfiltration technology is a widely used engineering strategy for fresh water production and water treatment. The major concern in many applications is the formation of a biological fouling layer leading to increased hydraulic resistance and flux decline during membrane operations. The growth of bacteria constituting such a biological layer implicates the formation of a multispecies biofilm and the consequent increase of operational costs for reactor management and cleaning procedures. To predict the biofilm growth and evolution during the filtration process, a one-dimensional continuous mo…
When an elastic object is dragged through a viscous fluid tangent to a rigid boundary, it experiences a lift force perpendicular to its direction of motion. An analogous lift mechanism occurs when a rigid symmetric object translates parallel to an elastic interface or a soft substrate. The induced lift force is attributed to an elastohydrodynamic coupling that arises from the breaking of the flow reversal symmetry induced by the elastic deformation of the translating object or the interface. Here we derive explicit analytical expressions for the quasi-steady state lift force exerted on a rigid…
Dynamic organization of the cytoskeletal filaments and rod-like proteins in the cell membrane and other biological interfaces occurs in many cellular processes. Previous modeling studies have considered the dynamics of a single rod on fluid planar membranes. We extend these studies to the more physiologically relevant case of a single filament moving in a spherical membrane. Specifically, we use a slender-body formulation to compute the translational and rotational resistance of a single filament of length $L$ moving in a membrane of radius $R$ and 2D viscosity $η_m$, and surrounded on its int…
This paper presents a model and numerical analysis (simulations) of transmembrane potential induced in biological cell membrane under the influence of externally applied electric field (i.e., electroporation). This model differs from the established models of electroporation in two distinct ways. Firstly, it incorporates the presence of cholesterol (~20% mole-fraction) in biological membrane. Secondly, it considers the distribution of pores as a function of the variation of transmembrane potential from one region of the cell to another. Formulation is based on the role of membrane tension and …
We investigated melting transitions in biological membranes in their native state that include their membrane proteins. These membranes originated from \textit{E. coli}, \textit{B. subtilis}, lung surfactant and nerve tissue from the spinal cord of several mammals. For some preparations, we studied the pressure, pH and ionic strength dependence of the transition. For porcine spine, we compared the transition of the native membrane to that of the extracted lipids. All preparations displayed melting transitions of 10-20 degrees below physiological or growth temperature, independent of the organi…
Roughly half of a cells proteins are located at or near the plasma membrane. In this restricted space the cell senses its environment, signals to its neighbors and ex-changes cargo through exo- and endocytotic mechanisms. Ligands bind to receptors, ions flow across channel pores, and transmitters and metabolites are transported against con-centration gradients. Receptors, ion channels, pumps and transporters are the molecular substrates of these biological processes and they constitute important targets for drug discovery. Total internal reflection fluorescence microscopy suppresses background…
Short peptides with antimicrobial activity have therapeutic potential for treating bacterial infections. Mechanisms of actions for antimicrobial peptides require binding the biological membrane of their target, which often represents a key mechanistic step. A multitude of data-driven approaches have been developed to predict potential antimicrobial peptide sequences; however, these methods are usually agnostic to the physical interactions between the peptide and the membrane. Towards developing higher throughput screening methodologies, here we use Markov State Modeling and all-atom molecular …
