Crowding-Regulated Binding of Divalent Biomolecules
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arXiv
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| Main Authors: | , , , |
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| Format: | Preprint |
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2024
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| _version_ | 1866929207516332032 |
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| author | Skóra, Tomasz Janssen, Mathijs Carlson, Andreas Kondrat, Svyatoslav |
| author_facet | Skóra, Tomasz Janssen, Mathijs Carlson, Andreas Kondrat, Svyatoslav |
| contents | Macromolecular crowding affects biophysical processes as diverse as diffusion, gene expression, cell growth, and senescence. Yet, there is no comprehensive understanding of how crowding affects reactions, particularly multivalent binding. Herein, we use scaled particle theory and develop a molecular simulation method to investigate the binding of monovalent to divalent biomolecules. We find that crowding can increase or reduce cooperativity--the extent to which the binding of a second molecule is enhanced after binding a first molecule--by orders of magnitude, depending on the sizes of the involved molecular complexes. Cooperativity generally increases when a divalent molecule swells and then shrinks upon binding two ligands. Our calculations also reveal that, in some cases, crowding enables binding that does not occur otherwise. As an immunological example, we consider Immunoglobulin G-antigen binding and show that crowding enhances its cooperativity in bulk but reduces it when an Immunoglobulin G binds antigens on a surface. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2401_06232 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | Crowding-Regulated Binding of Divalent Biomolecules Skóra, Tomasz Janssen, Mathijs Carlson, Andreas Kondrat, Svyatoslav Soft Condensed Matter Biological Physics Macromolecular crowding affects biophysical processes as diverse as diffusion, gene expression, cell growth, and senescence. Yet, there is no comprehensive understanding of how crowding affects reactions, particularly multivalent binding. Herein, we use scaled particle theory and develop a molecular simulation method to investigate the binding of monovalent to divalent biomolecules. We find that crowding can increase or reduce cooperativity--the extent to which the binding of a second molecule is enhanced after binding a first molecule--by orders of magnitude, depending on the sizes of the involved molecular complexes. Cooperativity generally increases when a divalent molecule swells and then shrinks upon binding two ligands. Our calculations also reveal that, in some cases, crowding enables binding that does not occur otherwise. As an immunological example, we consider Immunoglobulin G-antigen binding and show that crowding enhances its cooperativity in bulk but reduces it when an Immunoglobulin G binds antigens on a surface. |
| title | Crowding-Regulated Binding of Divalent Biomolecules |
| topic | Soft Condensed Matter Biological Physics |
| url | https://arxiv.org/abs/2401.06232 |