Biophysical properties of growing actin networks measured with atomic force microscopy
Bibliographic record
Abstract
The dynamic actin cytoskeleton plays a key role in a number of cellular processes including motility and shape change. Composed of individual filaments polymerized from actin monomers, the actin cytoskeleton is organized into a branched and cross-linked dendritic network by a diverse set of actin binding proteins. Directed growth of dendritic actin networks by monomer addition, such as at the leading edge of a crawling cell, generates the mechanical forces necessary for deforming the membrane during cell motility, endocytosis, and phagocytosis. Dysfunctional actin network regulation is associated with metastatic cancers, immune system disorders, and bacterial infection and pathogenesis. \tSignificant biochemical work over the past four decades has culminated into the dendritic nucleation model for actin network growth. This model summarizes the role of the major actin binding proteins, and interactions among them, that form and maintain a growing, dendritic actin network in crawling cells. Though actin biochemistry has been well studied, the force-generating ability and mechanical properties of growing dendritic actin networks that produce dynamic cellular shape changes remain unclear. This dissertation presents development of a unique measurement system for the purpose of understanding the biophysics of dendritic actin network growth. An experimental platform was built around a custom differential atomic force microscope by adapting a method for reconstituting actin network growth from cell-free extract in vitro to measure network force production and mechanics. The results described here demonstrate that dendritic actin networks possess a built-in force feedback system that enables active remodeling to support increasing forces. In addition, these networks exhibit the ability to reversibly stress soften under large loads, thereby avoiding catastrophic failure and retaining their underlying network structure as a molecular scaffold. These results have implications for understanding how crawling cells navigate through the physical barriers of the extracellular matrix and connective tissue in vivo while feeling a wide range of compressive forces.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".