Beyond calcium: cross-bridge binding regulates titin's contribution to muscle force
Bibliographic record
Abstract
Since the 1950s, muscle contraction has been explained by the sliding filament and cross-bridge theories involving actin and myosin. However, these theories do not account for certain muscle properties, such as residual force enhancement (rFE). The sarcomeric protein titin has been proposed to contribute to active force and rFE, but its role remains unclear. A leading hypothesis suggests that titin binds to actin, thereby shortening its spring-like segment, with calcium regulating this interaction. We investigated the roles of calcium and cross-bridge formation in titin mechanics by measuring the length of titin's PEVK region in sarcomeres during (i) passive stretch, (ii) active stretch with cross-bridge inhibition (via 2,3-butanedione monoxime, BDM) and (iii) active isometric contraction. PEVK lengths were similar for passive and cross-bridge-inhibited conditions but were longer for active contractions. Our results suggest that cross-bridge engagement, not calcium alone, modulates titin extensibility and passive force under physiological conditions.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".