Mechanical stress and network structure drive protein dynamics during cytokinesis

Cells undergo rapid shape changes during processes like cytokinesis and motility, which occur over seconds. These changes depend on molecular events that happen much faster, such as protein interactions and filament assembly. While signaling pathways are known to regulate cytoskeletal behavior, mechanical stresses also influence cytoskeletal protein accumulation. Myosin-II-based systems control contractility and shape during cytokinesis and under stress. In Dictyostelium, myosin II levels are regulated by feedback through the actin network, especially via the crosslinker cortexillin I. IQGAPs are key regulators in this system. However, the short-timescale dynamics of these proteins during cytokinesis and under mechanical stress remain unclear. This gap motivated the current study to examine how mechanical stress and network structure influence protein dynamics.

This study aimed to investigate the short-timescale dynamics of cytoskeletal proteins during cytokinesis and under mechanical stress. The goal was to understand how mechanical stress and network structure influence protein mobility and stability. The researchers focused on proteins like cortexillin I, IQGAP2, and myosin II, which are known to accumulate at the equator during cytokinesis. They used fluorescence recovery after photobleaching and fluorescence correlation spectroscopy to track protein dynamics. The study sought to determine whether protein mobility changes were due to biochemical events or structural changes in the cytoskeleton. By examining these dynamics, the researchers aimed to clarify how mechanical tuning affects contractile protein behavior and contributes to cytokinesis fidelity.

The researchers used fluorescence recovery after photobleaching (FRAP) and fluorescence correlation spectroscopy (FCS) to study cytoskeletal protein dynamics. These techniques allowed them to track protein mobility and recovery rates in living cells. They focused on proteins such as cortexillin I, IQGAP2, and myosin II, which are enriched at the equator during cytokinesis. Actin and polar crosslinkers were also analyzed for comparison. The study compared protein mobility at the furrow to that in the interphase cortex. The researchers examined whether changes in protein mobility were due to a single biochemical event or to broader structural changes in the cytoskeleton. By analyzing recovery rates and diffusion coefficients, they assessed how mechanical stress affects protein dynamics. The results were interpreted in the context of known mechanosensory systems involving myosin II and cortexillin I.

Equatorially enriched proteins like cortexillin I, IQGAP2, and myosin II showed significantly slower recovery rates compared to actin and polar crosslinkers. The mobility of equatorial proteins was much lower at the furrow than in the interphase cortex. This suggests that these proteins become stabilized during cytokinesis. The reduced mobility was not due to a single biochemical event but rather to global changes in cytoskeletal structure caused by mechanical stress. The study found that mechanical stress inhibits protein dynamics across the cytoskeletal network. This inhibition was observed in multiple proteins, indicating a widespread effect of mechanical tuning. The results support the idea that mechanical stress alters the cytoskeletal framework to regulate cell shape. These findings highlight the role of mechanical stress in controlling contractile protein dynamics during cytokinesis.

The authors propose that mechanical stress and network structure jointly regulate cytoskeletal protein dynamics during cytokinesis. Their findings suggest that mechanical stress leads to a global inhibition of protein mobility rather than a localized biochemical event. This inhibition stabilizes equatorial proteins like cortexillin I, IQGAP2, and myosin II at the furrow. The study supports the idea that mechanical tuning of contractile proteins enhances the robustness of the cytoskeletal framework. This framework is essential for maintaining cell shape and ensuring cytokinesis fidelity. The results align with prior knowledge of mechanosensory systems involving myosin II and cortexillin I. The authors suggest that structural changes in the cytoskeleton, rather than individual biochemical signals, drive the observed protein dynamics. These findings contribute to understanding how mechanical forces influence cellular processes.