Uncover mechanical principles of cellular function at the molecular level

In this experiment, a microtubule was immobilized to a biotinylated coverslip, and Ndc80 complexes, a key protein complex in the kinetochore structure, were attached to streptavidin-coated beads. By moving the bead with the C-Trap, we generated a rupture force between the microtubule and the kinetochore structure.

Researchers from David Barford’s team quantitatively assessed the outer kinetochore’s force resistance of the Dam1 and Ndc80 complexes. By comparing rupture forces of various mutations, they get a better understanding of which protein domains influence the kinetochore’s ability to withstand microtubule forces during cell division.

Measuring membrane tension is challenging as it requires precise manipulation and measurement of mechanical forces on individual tethers, which are small and difficult to control. With the C-Trap this could be resolved by combining optical tweezers for direct measurement of mechanical forces on individual tethers with optogenetics for local endogenous control of cell protrusion.

By using this combination of techniques, the lab of Bustamante was able to directly measure changes in membrane tension in response to mechanical forces generated by actin-driven protrusions. This allowed them to demonstrate that these protrusions generate rapid long-range membrane tension propagation in cells, which provides new insights into how cells respond to external stimuli and adapt to their environment.

First-generation bispecific T cell engagers (BTEs) have shown promise in preclinical models but often suffer from a short plasma half-life due to their small size and absence of an Fc domain. Additionally, limited tumor retention can lower local therapeutic concentrations and impede efficacy. Cancer cells can even adapt and evade immune targeting through antigen heterogeneity and loss, threatening sustained responses. The immunosuppressive tumor microenvironment further hinders T cell function and promotes therapeutic resistance. To develop an effective strategy, any cell engager must overcome these barriers to achieve robust, consistent targeting and immune activation.

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The following experiment highlights the forces and kinetics associated with filopodia formation. To assess the process, we studied Dictyostelium discoideum cells, a eukaryotic amoeba cell and model system that is commonly used to understand human cell processes.

The C-Trap can also manipulate small components inside of living multicellular organisms. We used the optical tweezers to manipulate intrinsic lipid droplets and study droplet fusion inside of Caenorhabditis elegans (roundworm).