scholarly journals Spatio-temporal mapping of mechanical force generated by macrophages during FcγR-dependent phagocytosis reveals adaptation to target stiffness

2020 ◽  
Author(s):  
Pablo Rougerie ◽  
Dianne Cox

ABSTRACTMacrophage phagocytosis is a strikingly flexible process central to pathogen clearance and is an attractive target for the development of anti-cancer immunotherapies. To harness the adaptability of phagocytosis, we must understand how macrophages can successfully deform their plasma membrane. While the signaling pathways and the molecular motors responsible for this deformation have been studied for many years, we only have limited insight into the mechanics that drive the formation of the phagocytic cup. Using Traction Force Microscopy (TFM), we have been able to characterize the spatio-temporal dynamics of mechanical forces generated in the course of FcγR-dependent frustrated phagocytosis and we determined whether this was affected by the stiffness of the potential phagocytic targets. We observed that frustrated phagocytosis is an atypical form of spreading where the cell deformation rate is unaffected by the substrate stiffness. Interestingly, the cell initially extends without forces being recorded then switches to a mode of pseudopod extension involving spatially organized force transmission. Importantly we demonstrate that macrophages adapt to the substrate stiffness primarily through a modulation of the magnitude of mechanical stress exerted, and not through modification of the mechanical stress kinetics or distribution. Altogether, we suggest that macrophage phagocytosis exhibits a clear resilience to variations of the phagocytic target stiffness and this is favored by an adaptation of their mechanical response.

2017 ◽  
Vol 28 (14) ◽  
pp. 1901-1911 ◽  
Author(s):  
Dennis W. Zhou ◽  
Ted T. Lee ◽  
Shinuo Weng ◽  
Jianping Fu ◽  
Andrés J. García

Focal adhesions (FAs) regulate force transfer between the cytoskeleton and ECM–integrin complexes. We previously showed that vinculin regulates force transmission at FAs. Vinculin residence time in FAs correlated with applied force, supporting a mechanosensitive model in which forces stabilize vinculin’s active conformation to promote force transfer. In the present study, we examined the relationship between traction force and vinculin–paxillin localization to single FAs in the context of substrate stiffness and actomyosin contractility. We found that vinculin and paxillin FA area did not correlate with traction force magnitudes at single FAs, and this was consistent across different ECM stiffness and cytoskeletal tension states. However, vinculin residence time at FAs varied linearly with applied force for stiff substrates, and this was disrupted on soft substrates and after contractility inhibition. In contrast, paxillin residence time at FAs was independent of local applied force and substrate stiffness. Paxillin recruitment and residence time at FAs, however, were dependent on cytoskeletal contractility on lower substrate stiffness values. Finally, substrate stiffness and cytoskeletal contractility regulated whether vinculin and paxillin turnover dynamics are correlated to each other at single FAs. This analysis sheds new insights on the coupling among force, substrate stiffness, and FA dynamics.


2020 ◽  
Vol 637 ◽  
pp. 117-140 ◽  
Author(s):  
DW McGowan ◽  
ED Goldstein ◽  
ML Arimitsu ◽  
AL Deary ◽  
O Ormseth ◽  
...  

Pacific capelin Mallotus catervarius are planktivorous small pelagic fish that serve an intermediate trophic role in marine food webs. Due to the lack of a directed fishery or monitoring of capelin in the Northeast Pacific, limited information is available on their distribution and abundance, and how spatio-temporal fluctuations in capelin density affect their availability as prey. To provide information on life history, spatial patterns, and population dynamics of capelin in the Gulf of Alaska (GOA), we modeled distributions of spawning habitat and larval dispersal, and synthesized spatially indexed data from multiple independent sources from 1996 to 2016. Potential capelin spawning areas were broadly distributed across the GOA. Models of larval drift show the GOA’s advective circulation patterns disperse capelin larvae over the continental shelf and upper slope, indicating potential connections between spawning areas and observed offshore distributions that are influenced by the location and timing of spawning. Spatial overlap in composite distributions of larval and age-1+ fish was used to identify core areas where capelin consistently occur and concentrate. Capelin primarily occupy shelf waters near the Kodiak Archipelago, and are patchily distributed across the GOA shelf and inshore waters. Interannual variations in abundance along with spatio-temporal differences in density indicate that the availability of capelin to predators and monitoring surveys is highly variable in the GOA. We demonstrate that the limitations of individual data series can be compensated for by integrating multiple data sources to monitor fluctuations in distributions and abundance trends of an ecologically important species across a large marine ecosystem.


Ecohydrology ◽  
2021 ◽  
Author(s):  
Qiongfang Li ◽  
Yuting Zhu ◽  
Qihui Chen ◽  
Yu Li ◽  
Jing Chen ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Liliana Barbieri ◽  
Huw Colin-York ◽  
Kseniya Korobchevskaya ◽  
Di Li ◽  
Deanna L. Wolfson ◽  
...  

AbstractQuantifying small, rapidly evolving forces generated by cells is a major challenge for the understanding of biomechanics and mechanobiology in health and disease. Traction force microscopy remains one of the most broadly applied force probing technologies but typically restricts itself to slow events over seconds and micron-scale displacements. Here, we improve >2-fold spatially and >10-fold temporally the resolution of planar cellular force probing compared to its related conventional modalities by combining fast two-dimensional total internal reflection fluorescence super-resolution structured illumination microscopy and traction force microscopy. This live-cell 2D TIRF-SIM-TFM methodology offers a combination of spatio-temporal resolution enhancement relevant to forces on the nano- and sub-second scales, opening up new aspects of mechanobiology to analysis.


2021 ◽  
Vol 13 (9) ◽  
pp. 4926
Author(s):  
Nguyen Duc Luong ◽  
Nguyen Hoang Hiep ◽  
Thi Hieu Bui

The increasing serious droughts recently might have significant impacts on socioeconomic development in the Red River basin (RRB). This study applied the variable infiltration capacity (VIC) model to investigate spatio-temporal dynamics of soil moisture in the northeast, northwest, and Red River Delta (RRD) regions of the RRB part belongs to territory of Vietnam. The soil moisture dataset simulated for 10 years (2005–2014) was utilized to establish the soil moisture anomaly percentage index (SMAPI) for assessing intensity of agricultural drought. Soil moisture appeared to co-vary with precipitation, air temperature, evapotranspiration, and various features of land cover, topography, and soil type in three regions of the RRB. SMAPI analysis revealed that more areas in the northeast experienced severe droughts compared to those in other regions, especially in the dry season and transitional months. Meanwhile, the northwest mainly suffered from mild drought and a slightly wet condition during the dry season. Different from that, the RRD mainly had moderately to very wet conditions throughout the year. The areas of both agricultural and forested lands associated with severe drought in the dry season were larger than those in the wet season. Generally, VIC-based soil moisture approach offered a feasible solution for improving soil moisture and agricultural drought monitoring capabilities at the regional scale.


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