Decoding Biomechanical Cues Based on DNA Sensors

Huang, Yihao; Chen, Ting; Chen, Xiaodie; Chen, Ximing; Zhang, Jialu; Liu, Sinong; Lu, Menghao; Chen, Chong; Ding, Xiangyu; Yang, Chaoyong; Huang, Ruiyun; Song, Yanling

doi:10.1002/smll.202310330

Cited by 3 publications

(1 citation statement)

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“…Fluorescence signals from a single fluorophore, or a fluorophore with a quencher, can also be used as readouts to detect DNA dissociation under force. Any molecular event exerting sufficient force to rupture the duplex will trigger dissociation of the two strands leading to loss of fluorescence due to the fluorophore leaving the imaging plane (22,24) or increased fluorescence in the case of a fluorophore-quencher pair (18).…”

Section: Introductionmentioning

confidence: 99%

In-SilicoAnalyses of Molecular Force Sensors for Mechanical Characterization of Biological Systems

Lopez,

Castro,

Sotomayor

2024

Preprint

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Mechanical forces play key roles in biological processes such as cell migration and sensory perception. In recent years molecular force sensors have been developed as tools for in situ force measurements. Here we use all-atom steered molecular dynamics simulations to predict and study the relationship between design parameters and mechanical properties for three types of molecular force sensors commonly used in cellular biological research: two peptide- and one DNA-based. The peptide-based sensors consist of a pair of fluorescent proteins, which can undergo Forster resonance energy transfer (FRET), linked by spider silk (GPGGA)n or synthetic (GGSGGS)n disordered regions. The DNA-based sensor consists of two fluorophore-labeled strands of DNA that can be unzipped or sheared upon force application with a FRET signal as readout of dissociation. We simulated nine sensors, three of each kind. After equilibration, flexible peptide linkers of three different lengths were stretched by applying forces to their N- and C-terminal Calpha atoms in opposite directions. Similarly, we equilibrated a DNA-based sensor and pulled on the phosphate atom of the terminal guanine of one strand and a selected phosphate atom on the other strand in the opposite direction. These simulations were performed at constant velocity (0.01 nm/ns - 10 nm/ns) and constant force (10 pN - 500 pN) for all versions of the sensors. Our results show how the force response of these sensors depends on their length, sequence, configuration and loading rate. Mechanistic insights gained from simulations analyses indicate that interpretation of experimental results should consider the influence of transient formation of secondary structure in peptide-based sensors and of overstretching in DNA-based sensors. These predictions can guide optimal fluorophore choice and facilitate the rational design of new sensors for use in protein, DNA, hybrid systems, and molecular devices.

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Section: Introductionmentioning

confidence: 99%