Molecular Force Sensors: From Fundamental Concepts toward Applications in Cell Biology

Abstract

Mechanical signals are central for the regulation of developmental, physiological, and pathological processes within biological systems. Force transduction across the cell–extracellular matrix (ECM) interface is highly crucial for regulating cell fate via mechanosensing and mechanotransduction cascades. The key molecules involved in these highly sophisticated processes have been identified in recent years. But little is still known about their interactions and in particular the molecular forces that determine these interactions. This is due to the limited availability of techniques that allow for investigating force propagation and mechanobiochemical signal conversion at the molecular level in live cells. In this progress report, currently available tools for measuring the molecular forces involved in cellular mechanosensing and mechanotransduction are summarized, specifically highlighting recent advances in the development of molecular force sensors (MFSs). MFSs convert the applied force into a fluorescence signal, allowing for a direct readout of tension with optical microscopy techniques. Moving from molecular design principles to applications of MFSs, important results are summarized, highlighting the new mechanistic information that has been obtained about mechanobiochemical processes at the cell–ECM interface. This progress report finishes with a critical discussion of current promises and limitations, providing perspectives for future research in this quickly evolving field

Structural determinants of coiled coil mechanics

“…Most interestingly, these parameters can be used to obtain CCs with similar thermodynamic stabilities that possess a different dynamic response to an externally applied force. Such systems will find application as molecular force sensors 41 or as physical hydrogel crosslinks, which show a pre-defined response to mechanical deformation.…”

Emulating Human Tissues and Organs: A Bioprinting Perspective Toward Personalized Medicine

“…Although early studies have been conducted on gold or glass surfaces, the technique is highly amendable for use in hydrogels as eluded to in a recent article from the group of Blank. 459 One of the major questions pertaining to the evolving field of bioprinting that remains, is to what extent spatial organization should be engineered and what should be left to the cells to self-organize? There is no doubt that most tissues require a strict organization to function but that functioning also depends on the interaction of the different cell types and tissue structures.…”

Fortified Coiled Coils: Enhancing Mechanical Stability with Lactam or Metal Staples

“…biomimetic hydrogels, [8] protein origami structures, [9] artificial membrane fusion domains [10] and molecular force sensors. [11] To tune the mechanical properties of synthetic CCs, a detailed understanding of their sequence-structure-mechanical relationships is crucial. We have recently shown that the helix propensity of the solvent-exposed amino acids affects the mechanical stability of a 4-heptad CC heterodimer when applying a shear force at two opposing termini.…”