Collective force generated by multiple biofilaments can exceed the sum of forces due to individual ones

Collective dynamics and force generation by cytoskeletal filaments are crucial in many cellular processes. Investigating growth dynamics of a bundle of N independent cytoskeletal filaments pushing against a wall, we show that chemical switching (ATP/GTP hydrolysis) leads to a collective phenomenon that is currently unknown. Obtaining force-velocity relations for different models that capture chemical switching, we show, analytically and numerically, that the collective stall force of N filaments is greater than N times the stall force of a single filament. Employing an exactly solvable toy model, we analytically prove the above result for N=2. We, further, numerically show the existence of this collective phenomenon, for N>=2, in realistic models (with random and sequential hydrolysis) that simulate actin and microtubule bundle growth. We make quantitative predictions for the excess forces, and argue that this collective effect is related to the non-equilibrium nature of chemical switching.Comment: New J. Phys., 201

Sufficient conditions for the additivity of stall forces generated by multiple filaments or motors

Molecular motors and cytoskeletal filaments work collectively most of the time under opposing forces. This opposing force may be due to cargo carried by motors or resistance coming from the cell membrane pressing against the cytoskeletal filaments. Some recent studies have shown that the collective maximum force (stall force) generated by multiple cytoskeletal filaments or molecular motors may not always be just a simple sum of the stall forces of the individual filaments or motors. To understand this excess or deficit in the collective force, we study a broad class of models of both cytoskeletal filaments and molecular motors. We argue that the stall force generated by a group of filaments or motors is additive, that is, the stall force of $N$ number of filaments (motors) is $N$ times the stall force of one filament (motor), when the system is in equilibrium at stall. Conversely, we show that this additive property typically does not hold true when the system is not at equilibrium at stall. We thus present a novel and unified understanding of the existing models exhibiting such non-addivity, and generalise our arguments by developing new models that demonstrate this phenomena. We also propose a quantity similar to thermodynamic efficiency to easily predict this deviation from stall-force additivity for filament and motor collectives.Comment: 14 pages, 7 figure

Molecular Interpretation of ACTH-β-Endorphin Coaggregation: Relevance to Secretory Granule Biogenesis

Peptide/protein hormones could be stored as non-toxic amyloid-like structures in pituitary secretory granules. ACTH and β-endorphin are two of the important peptide hormones that get co-stored in the pituitary secretory granules. Here, we study molecular interactions between ACTH and β-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-β-endorphin aggregate, ACTH alone cannot aggregate into amyloid under various plausible conditions. Using all atom molecular dynamics simulation we investigate the early molecular interaction events in the ACTH-β-endorphin system, β-endorphin-only system and ACTH-only system. We find that β-endorphin and ACTH formed an interacting unit, whereas negligible interactions were observed between ACTH molecules in ACTH-only system. Our data suggest that ACTH is not only involved in interaction with β-endorphin but also enhances the stability of mixed oligomers of the entire system

Stretching and Bending Fluctuations of Short DNA Molecules

AbstractRecent measurements of the distribution of end-to-end distance in short DNA molecules infer cooperative stretching fluctuations. The assumptions underlying the analysis can be questioned if transient, thermally induced defects producing a localized decrease in bending stiffness are present in thermal equilibrium, such as regions in which DNA melts locally (bubbles), sustains large-angle bends (kinks), or can locally transform into an alternative (S-DNA) state. We study a generalized discrete worm-like chain model for DNA, capable of describing these experiments, showing that the model yields accurate fits to available experimental data. Our results indicate that DNA bending arising from such localized defects, rather than solely stretching, can be an equal contributor to end-to-end distance fluctuations for 35-bp DNA and contributes nontrivially to such fluctuations at all scales below the persistence length. The analysis suggests that such fluctuations should exhibit a scale-dependent cooperativity, specifically relevant in determining the behavior of short chains, but which saturates rapidly to a length-independent value for longer DNA, to ensure a consistent physical description of DNA across multiple scales. Our approach provides a minimal, yet accurate, coarse-grained description of DNA at the subpersistence length scales of current experimental interest