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The viscous liquid surrounding a hair bundle dissipates energy and dampens oscillations, which poses a fundamental physical challenge to the high sensitivity and sharp frequency selectivity of hearing. To identify the mechanical forces at play, we constructed a detailed finite-element model of the hair bundle. Based on data from the hair bundle of the bullfrogs sacculus, this model treats the interaction of stereocilia both with the surrounding liquid and with the liquid in the narrow gaps between the individual stereocilia. The investigation revealed that grouping stereocilia in a bundle dramatically reduces the total drag. During hair-bundle deflections, the tip links potentially induce drag by causing small but very dissipative relative motions between stereocilia; this effect is offset by the horizontal top connectors that restrain such relative movements at low frequencies. For higher frequencies the coupling liquid is sufficient to assure that the hair bundle moves as a unit with a low total drag. This work reveals the mechanical characteristics originating from hair-bundle morphology and shows quantitatively how a hair bundle is adapted for sensitive mechanotransduction.
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The detection of sound begins when energy derived from acoustic stimuli deflects the hair bundles atop hair cells. As hair bundles move, the viscous friction between stereocilia and the surrounding liquid poses a fundamental challenge to the ears high sensitivity and sharp frequency selectivity. Part of the solution to this problem lies in the active process that uses energy for frequency-selective sound amplification. Here we demonstrate that a complementary part involves the fluid-structure interaction between the liquid within the hair bundle and the stereocilia. Using force measurement on a dynamically scaled model, finite-element analysis, analytical estimation of hydrodynamic forces, stochastic simulation and high-resolution interferometric measurement of hair bundles, we characterize the origin and magnitude of the forces between individual stereocilia during small hair-bundle deflections. We find that the close apposition of stereocilia effectively immobilizes the liquid between them, which reduces the drag and suppresses the relative squeezing but not the sliding mode of stereociliary motion. The obliquely oriented tip links couple the mechanotransduction channels to this least dissipative coherent mode, whereas the elastic horizontal top connectors stabilize the structure, further reducing the drag. As measured from the distortion products associated with channel gating at physiological stimulation amplitudes of tens of nanometres, the balance of forces in a hair bundle permits a relative mode of motion between adjacent stereocilia that encompasses only a fraction of a nanometre. A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction.
Nascent adhesions are submicron transient structures promoting the early adhesion of cells to the extracellular matrix. Nascent adhesions typically consist of several tens of integrins, and serve as platforms for the recruitment and activation of proteins to build mature focal adhesions. They are also associated with early stage signalling and the mechanoresponse. Despite their crucial role in sampling the local extracellular matrix, very little is known about the mechanism of their formation. Consequently, there is a strong scientific activity focused on elucidating the physical and biochemical foundation of their development and function. Precisely the results of this effort will be summarized in this article.
A highly organized and densely packed lattice of molecular machinery within the sarcomeres of muscle cells powers contraction. Although many of the proteins that drive contraction have been studied extensively, the mechanical impact of fluid shearing within the lattice of molecular machinery has received minimal attention. It was recently proposed that fluid flow augments substrate transport in the sarcomere, however, this analysis used analytical models of fluid flow in the molecular machinery that could not capture its full complexity. By building a finite element model of the sarcomere, we estimate the explicit flow field, and contrast it with analytical models. Our results demonstrate that viscous drag forces on sliding filaments are surprisingly small in contrast to the forces generated by single myosin molecular motors. This model also indicates that the energetic cost of fluid flow through viscous shearing with lattice proteins is likely minimal. The model also highlights a steep velocity gradient between sliding filaments and demonstrates that the maximal radial fluid velocity occurs near the tips of the filaments. To our knowledge, this is the first computational analysis of fluid flow within the highly structured sarcomere.
Endocytosis underlies many cellular functions including signaling and nutrient uptake. The endocytosed cargo gets redistributed across a dynamic network of endosomes undergoing fusion and fission. Here, a theoretical approach is reviewed which can explain how the microscopic properties of endosome interactions cause the emergent macroscopic properties of cargo trafficking in the endosomal network. Predictions by the theory have been tested experimentally and include the inference of dependencies and parameter values of the microscopic processes. This theory could also be used to infer mechanisms of signal-trafficking crosstalk. It is applicable to in vivo systems since fixed samples at few time points suffice as input data.
The internal cell wall structure of the bacterium Lactobacillus helveticus has been observed in situ in aqueous solution using an atomic force microscope (AFM). The AFM tip was used not only for imaging but presumably to remove mechanically large patches of the outer cell wall after appropriate chemical treatment, which typically leaves the bacteria alive. The surface exposed after such a surgery revealed ca. 26 nm thick twisted strands within the cell wall. The structure and location of the observed strands are consistent with the glycan backbone of peptidoglycan fibers that give strength to the cell wall. The found structural organization of these fibers has not been observed previously.
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