RT Journal Article
SR Electronic
T1 Cell-projection pumping: A hydrodynamic cell-stiffness dependent mechanism for cytoplasmic transfer between mammalian cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 531798
DO 10.1101/531798
A1 Hans Zoellner
A1 Navid Paknejad
A1 James Cornwell
A1 Belal Chami
A1 Yevgeniy Romin
A1 Vitaly Boykov
A1 Sho Fujisawa
A1 Elizabeth Kelly
A1 Garry W. Lynch
A1 Glynn Rogers
A1 Katia Manova
A1 Malcolm A.S. Moore
YR 2019
UL http://biorxiv.org/content/early/2019/01/27/531798.abstract
AB We earlier reported cytoplasmic fluorescence exchange between cultured human fibroblasts and malignant cells (MC). Current time-lapse microscopy showed most exchange was from fibroblasts into MC, with less in the reverse direction.Surprisingly, transfer was not via tunneling nanotubes, but by often branching cell-projections instead, and transfer events coincided with retraction of donor cell-projections. Increased hydrodynamic pressure in retracting cell-projections, normally returns cytoplasm to the cell body. We hypothesize ‘cell-projection pumping’ (CPP), where cytoplasm in retracting cell-projections equilibrates partially into adjacent recipient cells via temporary inter-cellular cytoplasmic continuities. Plausibility for CPP was explored via a mathematical model, which predicted preferential CPP into cells with lower cell stiffness, since pressure equilibrates towards least resistance.Predictions from the model were satisfied when fibroblasts were co-cultured with MC, and fluorescence exchange related with cell stiffness measured by atomic force microscopy. When transfer into 5000 simulated recipient MC or fibroblasts was studied in computer simulations, inputting experimental cell stiffness and donor cell fluorescence values, generated transfers to simulated recipient cells similar to those seen by experiment, including the expected inverse relationship between receptor cell stiffness and fluorescence uptake. We propose CPP as a novel mechanism in mammalian inter-cellular cytoplasmic transfer and communication.