Uncover mechanical principles of cellular function at the molecular level

Researchers from David Barford’s team (MRC-LMB Cambridge, UK) 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.

Further reading:

• Muir et al. Science (2023)

The complex structure of chromatin and its organization inchromosomes is driven and regulated by a plethora of biochemical and mechanicalcues, many of which remain to be fully understood. It becomes more and moreobvious that cross-talk between physical and chemical biochemical signals is akey aspect of this regulation. The C-Trap provides the ability to apply andmeasure precise mechanical forces while observing responses of the model systemof interest in real time via high-end microscopy and thus enables anunprecedented view on the principles underlying mechano-chemical regulation.

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An international research collaboration around Gijs Wuite(VU Amsterdam) examined chromosome mechanics under various conditions toquantify effects regulating their properties. They applied forces up to 350 pN,while shifting buffer conditions to observe immediate structural and mechanicalresponses in whole chromosomes. The unique integration of force applicationwith real-time fluorescence imaging proved to be ideal for capturing bothelastic (force-dependent) and viscous (time-dependent) responses inchromosomes, revealing previously inaccessible information about chromosomemechanics under biological conditions.

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Read more:

Witt et al. Nature Materials (2024)

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Shannon Yan and her coworkers in the lab of molecularbiophysics pioneer Carlos Bustamante (UC Berkeley, US) utilized the C-Trap foran innovative approach to the problem, combining optogenetics to directlycontrol localized actin-based protrusions or actomyosin contractions whilesimultaneously monitoring the propagation of membrane tension using a dual-trapoptical tweezers configuration. They revealed that:

• Actin-driven protrusions generate rapidlong-range membrane tension propagation in cells
• The actin cortex does not impede this tensionpropagation

This resolved some of the previous controversies about therole of the actin cortex in tension propagation and provided new insights intohow cells respond to external stimuli and adapt to their environment.

“A lot of times, seeing is believing. And so, when we detect any changes in the cell morphology or cell membrane tension, it’s always good to back up: to see in the image channel, by labeling, that the key players that we speculate are really doing the work, are correlating with the phenomenon that we detect.” - Shannon Yan PhD, Stanford University

Further reading

De Belly et al. Cell (2023)

By investigating the mechanical properties oftumor-associated macrophages (TAMs) and macrophages from heathy tissue, theteam of Alireza Mashaghi (Leiden University, NL) revealed that LeidenUniversity, NL) revealed that the cellular stiffness significantly differsbetween the two. Given the fact that immune cells constantly need to tune theirmechanical properties throughout their life cycle and journey through theorganism, this mechanical readout has great potential to support diagnosis butalso to explore new therapeutic approaches that target cellular mechanics.

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Further reading:  

Evers et al. Mater. Adv. (2024)
Evers et al. Advanced NanoBiomed Research (2022)
Sheikhhassani et al. Soft Matter (2022)
Evers et al. iScience (2022)

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