Tunneling Nanotubes between Cells Migrating in ECM Mimicking Fibrous Environments

Cancers

Amrinder S. Nain¹  Aniket Jana¹  Katherine Ladner²  Emil Lou² 

[1] Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA;Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA;

关键词: tunneling nanotubes;    membrane nanotubes;    cellular protrusions;    intercellular communication;    cell migration;    extracellular matrix;   

DOI  :  10.3390/cancers14081989

来源: DOAJ

【 摘 要 】

Tunneling nanotubes (TNTs) comprise a unique class of actin-rich nanoscale membranous protrusions. They enable long-distance intercellular communication and may play an integral role in tumor formation, progression, and drug resistance. TNTs are three-dimensional, but nearly all studies have investigated them using two-dimensional cell culture models. Here, we applied a unique 3D culture platform consisting of crosshatched and aligned fibers to fabricate synthetic suspended scaffolds that mimic the native fibrillar architecture of tumoral extracellular matrix (ECM) to characterize TNT formation and function in its native state. TNTs are upregulated in malignant mesothelioma; we used this model to analyze the biophysical properties of TNTs in this 3D setting, including cell migration in relation to TNT dynamics, rate of TNT-mediated intercellular transport of cargo, and conformation of TNT-forming cells. We found that highly migratory elongated cells on aligned fibers formed significantly longer but fewer TNTs than uniformly spread cells on crossing fibers. We developed new quantitative metrics for the classification of TNT morphologies based on shape and cytoskeletal content using confocal microscopy. In sum, our strategy for culturing cells in ECM-mimicking bioengineered scaffolds provides a new approach for accurate biophysical and biologic assessment of TNT formation and structure in native fibrous microenvironments.

【 授权许可】

Unknown