ICFO optical tweezers reveal details of cell aging and dynamics

07 Jan 2025

Beam-splitting technique measures viscoelasticity of biological materials to spot the changes underway.

A project led by Spain's ICFO research center has developed a novel optical tweezer arrangement able to assess the viscoelastic properties of biological materials.

Quantifying the mechanical responses of cell interiors or complex biomolecular materials should lead to a better understanding of cellular differentiation and aging, and could also accelerate drug discovery.

"In biology, changes in viscoelasticity can lead to severe diseases, such as cancers," commented ICFO.

"Knowing the viscoelasticity and other rheological properties of biological samples, such as intracellular organelles, cells or entire tissues, is central to understanding their physiological function."

Existing optical tweezer-based techniques aimed at the study of rheology face some practical hurdles, including the need for complicated experimental set-ups and perfectly aligned dual laser systems, noted the project. This is prohibitive for most laboratories, and few research sites worldwide have been able to employ this kind of technology in their studies.

The ICFO solution, published in Nature Nanotechnology, involves splitting a single laser beam into two near-instantaneous time-shared optical traps, one for driving active oscillations and the other for static displacement detection.

This time-shared optical tweezers microrheology (TimSOM) method requires only the one laser, simplifying the set-up and considerably enhancing the versatility of the technique.

"TimSOM is also accompanied by a step-by-step protocol on how to use it, which will facilitate the adoption of optical tweezers-based microrheology in the fields of molecular, cellular and developmental biology”, said ICFO's Michael Krieg.

Answering the fundamental questions

In trials, TimSOM was first applied to a protein condensate known to undergo an age-dependent transition from a liquid to a more solid state, the kind of phase transition thought to be related to neurodegenerative diseases. Viscoelasticity inside the material was substantially higher than that at the interface after maturation, which could suggest a potential mechanism for the maturation process.

The TimSOM method also measured viscoelasticity differences between cell nuclei and cytoplasm in zebrafish embryos, and assessed the relation between viscoelasticity and aging in the intestinal tissues of C. elegans nematodes, detecting mutations of the nuclear envelope that can accelerate the aging process.

"Because we used the same laser, our measurements were easy to conduct at different locations within the same living cells, which otherwise are notoriously difficult to perform," said Frederic Catala-Castro of ICFO. "In other words the single laser optical trap can be displaced at any position in the field of view, which enhances the spatiotemporal versatility of this method."

The TimSOM principle could now help to answer some of biology's fundamental questions about cell behavior and the energy that a cell requires in order to move, or investigate how deformation of mechano-sensitive protein condensates translates to the activation of neurons.

"TimSOM will help scientists in the field take a picture of biological mechanics, a stiffness map of a biomaterial," commented Michael Krieg. "That might allow us to finally answer these and many other long-lived questions in rheology."