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Living systems are intrinsically nonequilibrium: They use metabolically derived chemical energy to power their emergent dynamics and self-organization. A crucial driver of these dynamics is the cellular cytoskeleton, a defining example of an active material where the energy injected by molecular motors cascades across length scales, allowing the material to break the constraints of thermodynamic equilibrium and display emergent nonequilibrium dynamics only possible due to the constant influx of energy. Notwithstanding recent experimental advances in the use of local probes to quantify entropy production and the breaking of detailed balance, little is known about the energetics of active materials or how energy propagates from the molecular to emergent length scales. Here, we use a recently developed picowatt calorimeter to experimentally measure the energetics of an active microtubule gel that displays emergent large-scale flows. We find that only approximately one-billionth of the system's total energy consumption contributes to these emergent flows. We develop a chemical kinetics model that quantitatively captures how the system's total thermal dissipation varies with ATP and microtubule concentrations but that breaks down at high motor concentration, signaling an interference between motors. Finally, we estimate how energy losses accumulate across scales. Taken together, these results highlight energetic efficiency as a key consideration for the engineering of active materials and are a powerful step toward developing a nonequilibrium thermodynamics of living systems.

Cells are the basic units of all living matter which harness the flow of energy to drive the processes of life. While the biochemical networks involved in energy transduction are well-characterized, the energetic costs and constraints for specific cellular processes remain largely unknown. In particular, what are the energy budgets of cells? What are the constraints and limits energy flows impose on cellular processes? Do cells operate near these limits, and if so how do energetic constraints impact cellular functions? Physics has provided many tools to study nonequilibrium systems and to define physical limits, but applying these tools to cell biology remains a challenge. Physical bioenergetics, which resides at the interface of nonequilibrium physics, energy metabolism, and cell biology, seeks to understand how much energy cells are using, how they partition this energy between different cellular processes, and the associated energetic constraints. Here we review recent advances and discuss open questions and challenges in physical bioenergetics.

Cytoskeletal networks are foundational examples of active matter and central to self-organized structures in the cell. In vivo, these networks are active and densely crosslinked. Relating their large-scale dynamics to the properties of their constituents remains an unsolved problem. Here, we study an in vitro active gel made from aligned microtubules and XCTK2 kinesin motors. Using photobleaching, we demonstrate that the gel's aligned microtubules, driven by motors, continually slide past each other at a speed independent of the local microtubule polarity and motor concentration. This phenomenon is also observed, and remains unexplained, in spindles. We derive a general framework for coarse graining microtubule gels crosslinked by molecular motors from microscopic considerations. Using microtubule-microtubule coupling through a force-velocity relationship for kinesin, this theory naturally explains the experimental results: motors generate an active strain rate in regions of changing polarity, which allows microtubules of opposite polarities to slide past each other without stressing the material.

Cytoplasmic dynein-1 is a minus-end-directed motor protein that transports cargo over long distances and organizes the intracellular microtubule (MT) network. How dynein motor activity is harnessed for these diverse functions remains unknown. Here, we have uncovered a mechanism for how processive dynein-dynactin complexes drive MT-MT sliding, reorganization, and focusing, activities required for mitotic spindle assembly. We find that motors cooperatively accumulate, in limited numbers, at MT minus-ends. Minus-end accumulations drive MT-MT sliding, independent of MT orientation, resulting in the clustering of MT minus-ends. At a mesoscale level, activated dynein-dynactin drives the formation and coalescence of MT asters. Macroscopically, dynein-dynactin activity leads to bulk contraction of millimeter-scale MT networks, suggesting that minus-end accumulations of motors produce network-scale contractile stresses. Our data provide a model for how localized dynein activity is harnessed by cells to produce contractile stresses within the cytoskeleton, for example, during mitotic spindle assembly.

Presents an approach to the teaching of engineering that uses the ideas about the teaching of academic subject matter developed by D. Ausubel. Identifies a threat to higher education in the lack of knowledge of the relationship between research and teaching in engineering and science and remarks on the absence of a corpus of work related to subject teaching at the university level. (SLD)

Cells are the basic units of all living matter which harness the flow of energy to drive the processes of life. While the biochemical networks involved in energy transduction are well-characterized, the energetic costs and constraints for specific cellular processes remain largely unknown. In particular, what are the energy budgets of cells? What are the constraints and limits energy flows impose on cellular processes? Do cells operate near these limits, and if so how do energetic constraints impact cellular functions? Physics has provided many tools to study nonequilibrium systems and to define physical limits, but applying these tools to cell biology remains a challenge. Physical bioenergetics, which resides at the interface of nonequilibrium physics, energy metabolism, and cell biology, seeks to understand how much energy cells are using, how they partition this energy between different cellular processes, and the associated energetic constraints. Here we review recent advances and discuss open questions and challenges in physical bioenergetics. [ABSTRACT FROM AUTHOR]

Objective: We have shown previously that the amount grown through the year is related to short term changes in height and weight: good growth during the year was related to large but frequent gains in weight and large individual spurts in height. We have now analysed the relationship between annual weight gain (expressed in Δ̣ Weight SD score) and short-term growth pattern in height and weight in 43 schoolchildren (17 boys, 26 girls) aged 5.7-7.7 years. Methods: Height and weight of each child was measured three times per week over one academic year. A timed overnight urine was collected for urinary GH (uGH) excretion. Individual height and weight velocity curves were derived using locally-weighted, least-squares, kernel regression analysis. Urinary GH data were expressed as a daily average. Results: Weight velocity curves were characterised by 2-5 periods of weight gain, each lasting a mean 66 days, separated by 1-4 periods of weight loss, each lasting a mean 27 days. Δ Weight SD score was negatively correlated to mean uGH excretion (r=-0.43, p<0.005). In stepwise regression analysis, annual weight gain (Δ Weight SD score) was influenced by 5 factors: number (-) and mean length (-) of weight loss, mean (+) amplitude of weight gain, mean length of height velocity peak (+) and mean weekly uGH excretion (-), accounting for 58% of it's variability. Conclusions: We conclude that weight gain during a year is related mainly to short-term changes in weight but also to changes in height. Good weight gain during the year is related to large pulses of weight gain separated by infrequent short-lasting periods of weight loss and prolonged pulses of height gain. Additionally weekly uGH excretion, as a short-term marker of GH secretion, is low in those with good weight gain over the year. These data emphasise the close relationship between short-term changes in weight, height and GH secretion and their contribution to longer-term growth performance. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the regional difference in the prevalence of malnutrition in Saudi children., Methods: Data for this study were collected over 2 years (2004 and 2005). A cross-sectional representative sample of the Saudi population of healthy children below 5 years of age was used to calculate the prevalence of malnutrition. The study was carried out in the College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia. Body measurements of the weight, length, and height were performed according to standard recommendations. Standard deviation scores were determined using the Lambda, Mu, and Sigma (LMS) statistical methodology. The 1978 NCHS/WHO growth reference was used for the calculation of prevalence of underweight, wasting, and stunting defined as the proportion of children whose weight for age, weight for height, and height for age was below minus standard deviation (-2 SD) for Northern, Southwestern, and Central regions of the Kingdom of Saudi Arabia. Chi-square test was used to assess the difference in prevalence between regions, and a p<0.05 was considered significant., Results: The sample size of children <5 years of age in Central region was 5067, Southwestern 2285, and Northern 2933. The prevalence of underweight was 4%, 19.7% and 5.5%, that of wasting was 6.5%, 16.7% and 6.5% and of stunting was 6.4%, 13.2% and 6.4% in the Central, Southwestern, and Northern regions indicating a significantly-higher prevalence in Southwestern compared to other regions (p<0.001)., Conclusion: This report revealed a high prevalence of significant nutritional indicators in the Southwestern regions than in other regions. This finding indicates that this region should be given priority for further studies to identify causes, and to design health promotion programs.