PubMed Health⌕ Search

Biomedical subjects

Rony Granek

Publications and source records attributed to Rony Granek.

4 recordsLinked to original sources

Fractons in proteins: can they lead to anomalously decaying time autocorrelations?

Motivated by recent studies on the fractal nature of folded proteins, we analyze the time-dependent autocorrelation function < x (-->)(t).x(-->)(0) >of the distance between two points on a thermally vibrating fractal. Using fractons, the vibrational excitations of a fractal, we show that for both strongly underdamped and overdamped vibrations this correlation function decays anomalously, displaying a crossover from a nearly stretched exponential decay at short times to a slow algebraic decay at long times. Relationship to single molecule experiments is discussed.

Fractals↗

Nuclear localization signal peptides induce molecular delivery along microtubules.

Many essential processes in eukaryotic cells depend on regulated molecular exchange between its two major compartments, the cytoplasm and the nucleus. In general, nuclear import of macromolecular complexes is dependent on specific peptide signals and their recognition by receptors that mediate translocation through the nuclear pores. Here we address the question of how protein products bearing such nuclear localization signals arrive at the nuclear membrane before import, i.e., by simple diffusion or perhaps with assistance of cytoskeletal elements or cytoskeleton-associated motor proteins. Using direct single-particle tracking and detailed statistical analysis, we show that the presence of nuclear localization signals invokes active transport along microtubules in a cell-free Xenopus egg extract. Chemical and antibody inhibition of minus-end directed cytoplasmic dynein blocks this active movement. In the intact cell, where microtubules project radially from the centrosome, such an interaction would effectively deliver nuclear-targeted cargo to the nuclear envelope in preparation for import.

Actins↗

Fluorescence correlation spectroscopy close to a fluctuating membrane.

Compartmentalization of the cytoplasm by membranes should have a strong influence on the diffusion of macromolecules inside a cell, and we have studied how this could be reflected in fluorescence correlation spectroscopy (FCS) experiments. We derived the autocorrelation function measured by FCS for fluorescent particles diffusing close to a soft membrane, and show it to be the sum of two contributions: short timescale correlations come from the diffusion of the particles (differing from free diffusion because of the presence of an obstacle), whereas long timescale correlations arise from fluctuations of the membrane itself (which create intensity fluctuations by modulating the number of detected particles). In the case of thermal fluctuations this second type of correlation depends on the elasticity of the membrane. To illustrate this calculation, we report the results of FCS experiments carried out close to a vesicle membrane. The measured autocorrelation functions display very distinctly the two expected contributions, and allow both to recover the diffusion coefficient of the fluorophore and to characterize the membrane fluctuations in term of a bending rigidity. Our results show that FCS measurements inside cells can lead to erroneous values of the diffusion coefficient if the influence of membranes is not recognized.

Algorithms↗

Diffusion and directed motion in cellular transport.

We study the motion of a probe driven by microtubule-associated motors within a living eukaryotic cell. The measured mean square displacement, of engulfed 2 and 3 microm diameter microspheres shows enhanced diffusion scaling as t(3/2) at short times, with a clear crossover to ordinary or subdiffusive scaling, i.e., t(gamma) with gamma less than or equal to 1, at long times. Using optical tweezers we tried to move the engulfed bead within the cell in order to relate the anomalous diffusion scaling to the density of the network in which the bead is embedded. Results show that the larger beads, 2 and 3 microm diameter, must actively push the cytoskeleton filaments out of the way in order to move, whereas smaller beads of 1 microm diameter can be "rattled" within a cage. The 1 microm beads also perform an enhanced diffusion but with a smaller and less consistent exponent 1.2 approximately t(3/4). In the case of small beads, there may also be a Brownian contribution to the motion that results in a smaller exponent.

Biological Transport, Active↗