Regeneration
of injured neuronal areas is a big challenge owing
to the complex structure and function of the nervous system along
with the limited regeneration capacity of neural cells. Recent reports
show that patterned and functionalized scaffolds could control neural
cell directional growth. In this study, aligned nanofibers (ANFs)
were fabricated using a versatile and cost-effective approach, electrospinning,
and further processed to make a patterned hybrid scaffold (HANF).
The patterned scaffold had circular rings of ANFs reinforced in a
biocompatible gellan–gelatin hydrogel matrix to provide adequate
mechanical strength and contact guidance for adhesion and growth of
neural cells
in vitro
. Quercetin was loaded into
the nanofibrous scaffold to provide a functional agent that supported
regeneration of neural cells. The reinforced ANFs enhanced the mechanical
strength of the scaffold and provided a cylindrical nerve conduit
structure to support neuronal cell growth. The influence of scaffold
topology on cell behavior was assessed in
in vitro
cell culture conditions that revealed that the functionalized patterned
scaffolds favored directed neurite cell growth/extension with favored
cell culture morphology and showed no cytotoxicity toward neural cells.
The results ultimately indicated that the fabricated scaffold has
potential for guiding nerve tissue growth and can be used as nerve
regeneration scaffolds.
With the rise in need of sustainable mobility, persuasive design interventions holdan important place and have become an active research field in recent years. This paper aims to identify the problems faced by the people in using sustainable modes for daily travel and provide a solution to persuade people to choose sustainable transport options over private transport by using persuasive strategies on a personalized level. Data collection was carried out through a questionnaire filled by 90 participants and was tested using SPSS. Seven persuasive strategies have been used in designing a conceptual application prototype which has been further evaluated using Heuristic Analysis and Retrospective Think Aloud Protocol.The prototype classifies the persuasive strategies used for changing the behaviour in the domain of sustainable mobility while keeping in mind tailor-made features for the COVID-19 pandemic situation.
Cell migration through confined environments may induce a phenotypic transition to fast amoeboid (leader bleb-based) migration. However, the molecular mechanism(s) controlling this phenotypic transition remain poorly understood. Here, we show that regulation of intracellular calcium levels by the plasma membrane tension sensor, Piezo1, promotes the Leader Bleb-Based Migration (LBBM) of melanoma cells. Using a ratiometric assay, intracellular calcium is shown to rise with increasing levels of confinement. Chelation of extracellular and intracellular calcium by BAPTA and BAPTA-AM, respectively, inhibits LBBM. Moreover, in highly motile cells, we found intracellular calcium levels to be dramatically increased at the cell rear. Using the Piezo1 inhibitor, GsMTx4, and RNAi, we can inhibit the phenotypic transition to fast amoeboid (leader bleb-based) migration. Therefore, we wondered if Piezo1 through calcium/calmodulin activates Myosin Light Chain Kinase (MLCK) to promote actomyosin contractility and amoeboid migration. Using a microchannel based assay, we find that ROCK2 and not MLCK, promotes amoeboid migration. Altogether, our work reveals an unanticipated collaboration between Piezo1 and ROCK2 in amoeboid migrating melanoma cells.
Citation Format: Alexa Caruso, Neelakshi Kar, Jeremy Logue. Piezo1 and ROCK2 promote fast amoeboid migration in confined environments [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B021.
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