A reversible shearing DNA probe for visualizing mechanically strong receptors in living cells

Liu, Hongyun; Zhang, Chen; Hu, Yuru; Liu, Pengxiang; Sun, Feng; Chen, Wei; Zhang, Xinghua; Ma, Jie; Wang, Wen-Xu; Wang, Liang; Wu, Piyu; Zheng, Lina

doi:10.1038/s41556-021-00691-0

Cited by 49 publications

(63 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, the lack of tension signal on the RS probe shows that platelet integrin forces transient when compared to the longer time scales of for nucleic acid mechanical shearing of > 2-30 seconds. 22, 43…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Recently, the Liu group constructed a DNA-based reversible shearing probe in an attempt to overcome this limitation. 22 Using this reversible probe and other innovative tension sensor designs a more clear description of the forces associated with integrin activation have emerged indicating that F > 56 pN are central to focal adhesion maturation. 11,23,24,25 Interestingly, other studies have suggested that mechanosensor proteins not only detect and transduce force magnitude but also the force-extension history upon engaging the ligand.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Unbreakable DNA tension probes show that cell adhesion receptors detect the molecular force-extension curve of their ligands

Bender

Ogasawara

Kellner

et al. 2022

Preprint

View full text Add to dashboard Cite

Integrin receptors transduce the mechanical properties of the extracellular matrix. Past studies using DNA probes showed that integrins sense the magnitude of ligand forces with pN resolution. An open question is whether integrin receptors also sense the force-extension trajectory of their ligands. The challenge in addressing this question pertains to the lack of molecular probes that can control force-extension trajectories independently of force magnitude. To address this limitation, we synthesized two reversible DNA probes that fold with identical self-complementary domains but with different topologies. Thus, these probes unfold at the same steady-state force magnitude but following different kinetic pathways to reach the fully extended ssDNA state. Hairpin-like probes unzip with a low barrier of 14 pN while the pseudo-knot-like probes shear at 59 pN. Confirming that we had created probes with different barriers of unfolding, we quantified platelet integrin forces and measured 50-fold more tension signal with the unzipping probes over the shearing probes. In contrast, fibroblasts opened both probes to similar levels indicating more static forces. Surprisingly, fibroblast mechanotransduction markers, such as YAP levels, fibronectin production, actin organization, and integrin activation were significantly elevated on unzipping probes. This demonstrates that integrin receptors within focal adhesions sense the molecular force-extension profile of their ligands and not only the magnitude of equilibrium mechanical resistance.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Unbreakable DNA tension probes show that cell adhesion receptors detect the molecular force-extension curve of their ligands

Bender

Ogasawara

Kellner

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Most of cell studies have been performed at the human body temperature of 37 °C [11, 16–23]. As τ ( f ) of a TGT is highly sensitive to temperature (Supplemental Material VI [14]), we quantified τ ( f ) of four TGTs (Table I) at 37 °C, including three (7-bp, 11-bp and 15-bp) widely used in previous studies and one modified (13-bp) from the 15-bp TGT.…”

Section: Figmentioning

confidence: 99%

The mechanical stability of Tension Gauge Tethers

Liu

Yao

et al. 2022

Preprint

View full text Add to dashboard Cite

Mechanotransduction of cells, a time-taking process, relies on responding to tension transmitted along various supramolecular linkages. The minimal lifetimes of the linkages needed for proper mechanotransduction remain poorly understood. We propose that such information can be provided using tension-dependent lifetime sensors that undergo irreversible tension-dependent dissociation. We quantified the tension-dependent lifetime of DNA-based Tension Gauge Tethers. Comparing it with the observations from previous cell studies, the minimal lifetime of individual integrin-RGD linkage needed for cell spreading was determined to be tens of seconds over the physiological tension range.

show abstract

“…[ 165c ] To overcome the drawback of DNA‐based MFPs, in which it is rarely possible to measure ligand‐receptor interactions in a higher force regime (>20 pN), Li et al developed a reversible shearing DNA‐based MFP that can achieve a high measurable force of 60 pN with force resolution to the piconewton scale. [ 170 ] Reversibly probing relatively high forces generated by ligands without destabilizing or disrupting the adhesion site empowers these reversible shearing DNA‐based MFPs to directly reveal the differences between load‐bearing integrins. Besides the improvement in the maximum measurable force and force resolution, the temporal resolution of DNA‐based MFPs has also been dramatically advanced.…”

Section: Mfpsmentioning

confidence: 99%

Biophysical Approaches for Applying and Measuring Biological Forces

et al. 2021

View full text Add to dashboard Cite

Over the past decades, increasing evidence has indicated that mechanical loads can regulate the morphogenesis, proliferation, migration, and apoptosis of living cells. Investigations of how cells sense mechanical stimuli or the mechanotransduction mechanism is an active field of biomaterials and biophysics. Gaining a further understanding of mechanical regulation and depicting the mechanotransduction network inside cells require advanced experimental techniques and new theories. In this review, the fundamental principles of various experimental approaches that have been developed to characterize various types and magnitudes of forces experienced at the cellular and subcellular levels are summarized. The broad applications of these techniques are introduced with an emphasis on the difficulties in implementing these techniques in special biological systems. The advantages and disadvantages of each technique are discussed, which can guide readers to choose the most suitable technique for their questions. A perspective on future directions in this field is also provided. It is anticipated that technical advancement can be a driving force for the development of mechanobiology.

show abstract

A reversible shearing DNA probe for visualizing mechanically strong receptors in living cells

Cited by 49 publications

References 45 publications

Unbreakable DNA tension probes show that cell adhesion receptors detect the molecular force-extension curve of their ligands

Unbreakable DNA tension probes show that cell adhesion receptors detect the molecular force-extension curve of their ligands

The mechanical stability of Tension Gauge Tethers

Biophysical Approaches for Applying and Measuring Biological Forces

Contact Info

Product

Resources

About