The morphological role of ligand inhibitors in blocking receptor- and clathrin-mediated endocytosis
Bibliographic record
Abstract
Cells often internalize particles through endocytic pathways that involve the binding between cell receptors and particle ligands, which drives the cell membrane to wrap the particle into a delivery vesicle. Previous findings showed that receptor-mediated endocytosis is impossible for spherical particles smaller than a minimum size because of the energy barrier created by membrane bending. In this study, we investigate the morphological role of ligand inhibitors in blocking endocytosis, inspired by antibodies that inhibit virus ligands to prevent infection. While ligand inhibitors have the obvious effect of reducing the driving force due to adhesion, they also have a nontrivial (morphological) impact on the entropic and elastic energy of the system. We determine the necessary conditions for endocytosis by considering the additional energy barrier due to the membrane bending to wrap the inhibiting protrusions. We find that inhibitors increase the minimum radius previously reported, depending on their density and size. In addition, we extend this result to the case of clathrin-mediated endocytosis, which is the most common pathway for virus entry. The assembly of a clathrin coat with a spontaneous curvature increases the energy barrier and sets a maximum particle size (in agreement with experimental observations on spherical particles). Our investigation suggests that morphological considerations can inform the optimal design of neutralizing viral antibodies and new strategies for targeted nanomedicine.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".