Mechano-transduction: from molecules to tissues.

External forces play complex roles in cell organization, fate, and homeostasis. Changes in these forces, or how cells respond to them, can result in abnormal embryonic development and diseases in adults. How cells sense and respond to these mechanical stimuli requires an understanding of the biophysical principles that underlie changes in protein conformation and result in alterations in the organization and function of cells and tissues. Here, we discuss mechano-transduction as it applies to protein conformation, cellular organization, and multi-cell (tissue) function

The Caloric Cost of Self-Paced Exercise in Full Body Tabata, Treadmill Running Tabata, and Continuous Running

Weight management via exercise is critical in both athletic and general populations. It is unclear what modality of exercise elicits the greatest caloric efficiency. PURPOSE: To compare the energy expenditure of three different exercise regimens when performed at a self-selected pace. METHODS: Recreationally active men (n=3) and women (n=4) performed 3 separate exercise bouts at a self-selected pace: total body Tabata (TBT), treadmill running Tabata (TRT), and continuous running (CONT) in a counterbalanced manner with at least 48h between bouts. Trials consisted of a 10-minute rest period, 5-minute warmup, 25-minute exercise bout, and a 25-minute recovery period. TBT consisted of repeated cycles of body calisthenics for 20 seconds with 10-seconds rest in between. TRT consisted of repeated sprints on a treadmill in the same manner as TBT. CONT was a continuous exercise bout on a treadmill. In TRT and CONT trials, participants could manipulate treadmill speed in 5-minute increments. For each bout, participants wore a portable metabolic analyzer (CosMed K-5) during the rest, warmup, exercise, and recovery period to assess energy expenditure (EE), respiratory exchange ratio (RER), fat oxidation (FO), and excess post-exercise consumption (EPOC). Heart rate (HR) was recorded during exercise and recovery in 5-minute increments. Significant differences (pRESULTS: There were no significant differences in average HR (bpm) during exercise (TBT = 174.9±6.1; TRT = 182.1±5.9; CONT = 181.4±8.4) or during recovery. EE during exercise was significantly higher in CONT (356.7±82.9 kcals) than TRT (312.8±70.0 kcals; p=0.007, ES=.56) and TBT (266.3±63.9 kcals; p=0.001, ES=1.2). Additionally, EE during exercise was significantly higher in TRT than TBT (p=.005, ES=.59). During minutes 0-25 of recovery, no significant differences were found in EE or fat oxidation. However, in minutes 10-25 of recovery, TBT (31.7±8.7 kcals) was significantly higher in EE than CONT (26.0±7.0 kcals; p=0.009, ES=.69) and had a higher rate of FO (0.19±0.07 g∙min-1) than TRT (0.12±0.06 g∙min-1; p=0.013, ES=1.03) and CONT (0.13±0.05 g∙min-1; p=0.036, ES=.87). During exercise, RER was significantly higher in TBT (1.00±0.04) than TRT (0.94±0.03; p=0.019, ES=1.28), but there were no differences during recovery. EPOC at minutes 0-25 of recovery was significantly higher in TBT (3.7±1.8 L∙min-1) than TRT (2.0±1.2 L∙min-1; p=0.039). CONCLUSION: At a self-selected pace, intensity was similar across trials. When compared to TBT and TRT, CONT burned more calories during exercise, implying that CONT burns more calories when matched for time and intensity. However, TBT elicited higher EE and FO while recovering, possibly due to TBT relying more on carbohydrates as evidenced by the higher exercise RER. The increased use of fat during recovery helps replenish glycogen stores and facilitates the body’s full recovery to pre-exercise levels. Future studies should examine the metabolic responses that take place during the performance of other self-paced exercise modalities to determine the most calorically efficient exercise

Evaluating the Applicability of the Fokker-Planck Equation in Polymer Translocation: A Brownian Dynamics Study

Brownian dynamics (BD) simulations are used to study the translocation dynamics of a coarse-grained polymer through a cylindrical nanopore. We consider the case of short polymers, with a polymer length, N, in the range N=21-61. The rate of translocation is controlled by a tunable friction coefficient, gamma_{0p}, for monomers inside the nanopore. In the case of unforced translocation, the mean translocation time scales with polymer length N as ~ (N-N_p)^alpha, where N_p is the average number of monomers in the nanopore. The exponent approaches the value alpha=2 when the pore friction is sufficiently high, in accord with the prediction for the case of the quasi-static regime where pore friction dominates. In the case of forced translocation, the polymer chain is stretched and compressed on the cis and trans sides, respectively, for low gamma_{0p}. However, the chain approaches conformational quasi-equilibrium for sufficiently large gamma_{0p}. In this limit the observed scaling of with driving force and chain length supports the FP prediction that is proportional to N/f_d for sufficiently strong driving force. Monte Carlo simulations are used to calculate translocation free energy functions for the system. The free energies are used with the Fokker-Planck equation to calculate translocation time distributions. At sufficiently high gamma_{0p}, the predicted distributions are in excellent agreement with those calculated from the BD simulations. Thus, the FP equation provides a valid description of translocation dynamics for sufficiently high pore friction for the range of polymer lengths considered here. Increasing N will require a corresponding increase in pore friction to maintain the validity of the FP approach. Outside the regime of low N and high pore friction, the polymer is out of equilibrium, and the FP approach is not valid.Comment: 13 pages, 11 figure

Parallel fabrication and single-electron charging of devices based on ordered, two-dimensional phases of organically functionalized metal nanocrystals

A parallel technique for fabricating single-electron, solid-state capacitance devices from ordered, two-dimensional closest-packed phases of organically functionalized metal nanocrystals is presented. The nanocrystal phases were prepared as Langmuir monolayers and subsequently transferred onto Al-electrode patterned glass substrates for device construction. Alternating current impedance measurements were carried out to probe the single-electron charging characteristics of the devices under both ambient and 77 K conditions. Evidence of a Coulomb blockade and step structure reminiscent of a Coulomb staircase is presented

Spatial distribution of cell-cell and cell-ECM adhesions regulates force balance while main-taining E-cadherin molecular tension in cell pairs.

Mechanical linkage between cell-cell and cell-extracellular matrix (ECM) adhesions regulates cell shape changes during embryonic development and tissue homoeostasis. We examined how the force balance between cell-cell and cell-ECM adhesions changes with cell spread area and aspect ratio in pairs of MDCK cells. We used ECM micropatterning to drive different cytoskeleton strain energy states and cell-generated traction forces and used a Förster resonance energy transfer tension biosensor to ask whether changes in forces across cell-cell junctions correlated with E-cadherin molecular tension. We found that continuous peripheral ECM adhesions resulted in increased cell-cell and cell-ECM forces with increasing spread area. In contrast, confining ECM adhesions to the distal ends of cell-cell pairs resulted in shorter junction lengths and constant cell-cell forces. Of interest, each cell within a cell pair generated higher strain energies than isolated single cells of the same spread area. Surprisingly, E-cadherin molecular tension remained constant regardless of changes in cell-cell forces and was evenly distributed along cell-cell junctions independent of cell spread area and total traction forces. Taken together, our results showed that cell pairs maintained constant E-cadherin molecular tension and regulated total forces relative to cell spread area and shape but independently of total focal adhesion area

Histone Hypervariants H2A.Z.1 and H2A.Z.2 Play Independent and Context-Specific Roles in Neuronal Activity-Induced Transcription of Arc/Arg3.1 and Other Immediate Early Genes.

The histone variant H2A.Z is an essential and conserved regulator of eukaryotic gene transcription. However, the exact role of this histone in the transcriptional process remains perplexing. In vertebrates, H2A.Z has two hypervariants, H2A.Z.1 and H2A.Z.2, that have almost identical sequences except for three amino acid residues. Due to such similarity, functional specificity of these hypervariants in neurobiological processes, if any, remain largely unknown. In this study with dissociated rat cortical neurons, we asked if H2A.Z hypervariants have distinct functions in regulating basal and activity-induced gene transcription. Hypervariant-specific RNAi and microarray analyses revealed that H2A.Z.1 and H2A.Z.2 regulate basal expression of largely nonoverlapping gene sets, including genes that code for several synaptic proteins. In response to neuronal activity, rapid transcription of our model gene Arc is impaired by depletion of H2A.Z.2, but not H2A.Z.1. This impairment is partially rescued by codepletion of the H2A.Z chaperone, ANP32E. In contrast, under a different context (after 48 h of tetrodotoxin, TTX), rapid transcription of Arc is impaired by depletion of either hypervariant. Such context-dependent roles of H2A.Z hypervariants, as revealed by our multiplexed gene expression assays, are also evident with several other immediate early genes, where regulatory roles of these hypervariants vary from gene to gene under different conditions. Together, our data suggest that H2A.Z hypervariants have context-specific roles that complement each other to mediate activity-induced neuronal gene transcription

Impact ionisation electroluminescence in planar GaAs-based heterostructure Gunn diodes:Spatial distribution and impact of doping nonuniformities

When biased in the negative differential resistance regime, electroluminescence (EL) is emitted from planar GaAs heterostructure Gunn diodes. This EL is due to the recombination of electrons in the device channel with holes that are generated by impact ionisation when the Gunn domains reach the anode edge. The EL forms non-uniform patterns whose intensity shows short-range intensity variations in the direction parallel to the contacts and decreases along the device channel towards the cathode. This paper employs Monte Carlo models, in conjunction with the experimental data, to analyse these non-uniform EL patterns and to study the carrier dynamics responsible for them. It is found that the short-range lateral (i.e., parallel to the device contacts) EL patterns are probably due to non-uniformities in the doping of the anode contact, illustrating the usefulness of EL analysis on the detection of such inhomogeneities. The overall decreasing EL intensity towards the anode is also discussed in terms of the interaction of holes with the time-dependent electric field due to the transit of the Gunn domains. Due to their lower relative mobility and the low electric field outside of the Gunn domain, freshly generated holes remain close to the anode until the arrival of a new domain accelerates them towards the cathode. When the average over the transit of several Gunn domains is considered, this results in a higher hole density, and hence a higher EL intensity, next to the anode