Molecular dynamics model of mechanophore sensors for biological force measurement
Cellular forces regulate an untold spectrum of living processes, such as cell migration, gene expression, and ion conduction. However, a quantitative description of mechanical control remains elusive due to the lack of general, live-cell tools to measure discrete forces between biomolecules. Here we...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402417209X |
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| author | Sumit Mittal Rongsheng E. Wang Robert Ros Alison E. Ondrus Abhishek Singharoy |
| author_facet | Sumit Mittal Rongsheng E. Wang Robert Ros Alison E. Ondrus Abhishek Singharoy |
| author_sort | Sumit Mittal |
| collection | DOAJ |
| description | Cellular forces regulate an untold spectrum of living processes, such as cell migration, gene expression, and ion conduction. However, a quantitative description of mechanical control remains elusive due to the lack of general, live-cell tools to measure discrete forces between biomolecules. Here we introduce a computational pipeline for force measurement that leverages well-defined, tunable release of a mechanically activated small molecule fluorophore. These sensors are characterized using a multiscale approach combining equilibrium and steered QM/MM molecular dynamics models to capture the chemical, mechanical, and conformational transitions underlying force activation thresholds on a nano Newton scale. We find that chemical modification of the mechanophore and variation of its biomolecular tethers can tune the rate-determining step for fluorophore release and adjust the mechanochemical activation barrier. The models offer a new molecular framework for calibrated, programmable biomolecular force reporting within the live-cell regime, opening new opportunities to study mechanical phenomena in biological systems. |
| format | Article |
| id | doaj-art-348d467cede3492e8b55e0194c59d64d |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-348d467cede3492e8b55e0194c59d64d2025-01-17T04:50:25ZengElsevierHeliyon2405-84402025-01-01111e41178Molecular dynamics model of mechanophore sensors for biological force measurementSumit Mittal0Rongsheng E. Wang1Robert Ros2Alison E. Ondrus3Abhishek Singharoy4School of Advanced Sciences and Languages, VIT Bhopal University, Kothrikalan, Sehore, Madhya Pradesh, 466114, India; Corresponding author. School of Advanced Sciences and Languages, VIT Bhopal University, Kothrikalan, Sehore, Madhya Pradesh, 466114, India.Department of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USADepartment of Physics, Arizona State University, Tempe, AZ, 85287, USA; Center for Single Molecule Biophysics, The Biodesign Institute, Arizona State University, Tempe, AZ, 85287, USA; Center for Biological Physics, Arizona State University, Tempe, AZ, 85287, USADepartment of Chemistry and Pharmaceutical Sciences, University of Illinois Chicago, 900 W Taylor St, Science & Engineering Laboratories West South Building #608 Room 2230, Chicago, IL, 60607, USA; Corresponding author.School of Molecular Sciences, Arizona State University, Tempe, AZ, 85287, USA; Corresponding author.Cellular forces regulate an untold spectrum of living processes, such as cell migration, gene expression, and ion conduction. However, a quantitative description of mechanical control remains elusive due to the lack of general, live-cell tools to measure discrete forces between biomolecules. Here we introduce a computational pipeline for force measurement that leverages well-defined, tunable release of a mechanically activated small molecule fluorophore. These sensors are characterized using a multiscale approach combining equilibrium and steered QM/MM molecular dynamics models to capture the chemical, mechanical, and conformational transitions underlying force activation thresholds on a nano Newton scale. We find that chemical modification of the mechanophore and variation of its biomolecular tethers can tune the rate-determining step for fluorophore release and adjust the mechanochemical activation barrier. The models offer a new molecular framework for calibrated, programmable biomolecular force reporting within the live-cell regime, opening new opportunities to study mechanical phenomena in biological systems.http://www.sciencedirect.com/science/article/pii/S240584402417209XMechanophoreQM/MM simulationsBiosensorsPolymer mechanochemistryDFT |
| spellingShingle | Sumit Mittal Rongsheng E. Wang Robert Ros Alison E. Ondrus Abhishek Singharoy Molecular dynamics model of mechanophore sensors for biological force measurement Heliyon Mechanophore QM/MM simulations Biosensors Polymer mechanochemistry DFT |
| title | Molecular dynamics model of mechanophore sensors for biological force measurement |
| title_full | Molecular dynamics model of mechanophore sensors for biological force measurement |
| title_fullStr | Molecular dynamics model of mechanophore sensors for biological force measurement |
| title_full_unstemmed | Molecular dynamics model of mechanophore sensors for biological force measurement |
| title_short | Molecular dynamics model of mechanophore sensors for biological force measurement |
| title_sort | molecular dynamics model of mechanophore sensors for biological force measurement |
| topic | Mechanophore QM/MM simulations Biosensors Polymer mechanochemistry DFT |
| url | http://www.sciencedirect.com/science/article/pii/S240584402417209X |
| work_keys_str_mv | AT sumitmittal moleculardynamicsmodelofmechanophoresensorsforbiologicalforcemeasurement AT rongshengewang moleculardynamicsmodelofmechanophoresensorsforbiologicalforcemeasurement AT robertros moleculardynamicsmodelofmechanophoresensorsforbiologicalforcemeasurement AT alisoneondrus moleculardynamicsmodelofmechanophoresensorsforbiologicalforcemeasurement AT abhisheksingharoy moleculardynamicsmodelofmechanophoresensorsforbiologicalforcemeasurement |