Potential Hydrodynamic Cytoplasmic Transfer between Mammalian Cells: Cell-Projection Pumping

Abstract

Fig. S5 Holotomographic images at single optical levels of a co-culture of fibroblasts cocultured with SAOS-2 showing the presence of branching cell-projections consistent with those inferred from CLSM observations. Page 21: Fig. S6 Sequential holotomographic time-lapse images at a single optical level of a coculture of fibroblasts with SAOS-2, showing rapid movement of a cell projections between timepoints. Several separate cell projections were evident at the interface between two adjacent cells. Page 22: Fig. S7 Flattened optical confocal microscopy projection and two optical levels of fibroblasts co-cultured for 24 h with MM200-B12, showing the presence of organelles derived from different cells on different optical levels. Page 23: Fig. S8 Flattened optical confocal microscopy projections of fibroblasts co-cultured for 24 Hr with MM200-B12, showing tunneling nanotubes. Page 24: Fig. S9 Holotomography demonstrating tunneling nanotubes in a co-culture of fibroblasts with SAOS-2 at a single time point and four separate optical levels. Page 25: Fig. S10 Flattened optical confocal microscopy projection and 6 optical levels of fibroblasts co-cultured with MM200-B12, showing close entwining of fibroblast processes with malignant cells in absence of non-specific transfer of fibroblast label. Page 26: Fig. S11 Scattergrams from computer simulations showing the relationship between stiffness of individual receptor cells and fluorescence acquired from donor cells, where stiffness of the two cell populations is varied, as well as the median CPP volume exchange for each simulation.

Cell-Projection Pumping of Fibroblast Contents into Osteosarcoma SAOS-2 Cells Correlates with Increased SAOS-2 Proliferation and Migration, as well as Altered Morphology

“…We earlier described the exchange of membrane, organelles and cytoplasmic protein between cultured human fibroblasts and cancer cells [ 1 , 2 , 3 ] and others have made similar observations [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. The uptake of cellular contents by such transfers may be via exosomes, tunnelling nanotubes, or a mechanism we recently reported and termed ‘cell-projection pumping’ and these can significantly change the phenotype of acceptor cells [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. The transfer of mitochondria appears especially significant and can confer chemotherapy resistance to cancer cells [ 4 , 6 …”

“…The transfer of mitochondria appears especially significant and can confer chemotherapy resistance to cancer cells [ 4 , 6 , 7 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. However, we are made wary of ascribing most phenotypic effects to mitochondrial exchange by our observation that, in addition to mitochondria, there is also bulk transfer of cytoplasmic proteins, plasma membrane-bound alkaline phosphatase and organelles smaller than mitochondria [ 1 , 2 , 3 ].…”

“…Tunnelling nanotubes are delicate tube-like structures that establish cytoplasmic continuity between often distant cells and, in two-dimensional cell cultures, appear as pipe-like structures suspended above the culture surface [ 8 , 9 , 10 , 14 , 15 , 28 , 29 , 30 ]. Cell-projection pumping is a hydrodynamic mechanism, whereby retracting cell-projections inject their cytoplasmic contents into adjacent cells [ 3 ]. A recent independent report supports the novel cell-projection pumping mechanism and relates chemotherapy resistance of multiple myeloma cells to the uptake of mitochondria from co-cultured bone marrow-derived stromal cells [ 21 ].…”

“…An outline of cell-projection pumping is provided because the mechanism has only recently been described [ 3 ]. In brief, most cells extend and retract cell-projections as part of their normal function.…”

Holotomographic microscopy: A new approach to detect apoptotic cell features

“…Since plasma membrane morphological changes can be correlated to modifications in cellular functions (such as neoplastic changes, death, differentiation, or interactions with the extracellular space), HT could be suitable to study these biological aspects (Jeught, Sijbers, & Dirckx, 2015;Kim et al, 2014;Kim et al, 2017;Zoellner et al, 2020).…”