Intercellular nanotubes: insights from imaging studies and beyond

Hurtig, Johan; Chiu, Daniel T.; Önfelt, Björn

doi:10.1002/wnan.80

Cited by 79 publications

(92 citation statements)

References 108 publications

(194 reference statements)

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“…Single-molecule transport and spectroscopy have been reported 66 , and fundamental properties and the dynamics of lipid nanotubes 38,42,67 , which have an important role in intercellular transport and communication 5 , have been investigated. Limitations come partly from the properties of the soft-matter materials used to build these networks and partly from restrictions on experimental conditions.…”

Section: Applications and Limitationsmentioning

confidence: 99%

“…Intercellular nanotubes (ICNs) formed from filopodial structures or after separation of tight cell-cell contacts mediate transport processes between cells. For example, diffusion of inositol triphosphate through nanotubes possibly mediates calcium signaling between macrophages, a gradient of membrane tension can induce transport of membrane patches and surface proteins, and molecular motors can transport organelles along filamentous actin in ICNs [5][6][7] . Land plants have developed plasmodesmata, a form of sophisticated membrane channel used to span the rigid cell walls to mediate the cell-to-cell exchange of signaling molecules 8 .…”

Section: Introductionmentioning

confidence: 99%

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Generation of phospholipid vesicle-nanotube networks and transport of molecules therein

et al. 2011

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We describe micromanipulation and microinjection procedures for the fabrication of soft-matter networks consisting of lipid bilayer nanotubes and surface-immobilized vesicles. these biomimetic membrane systems feature unique structural flexibility and expandability and, unlike solid-state microfluidic and nanofluidic devices prepared by top-down fabrication, they allow network designs with dynamic control over individual containers and interconnecting conduits. the fabrication is founded on self-assembly of phospholipid molecules, followed by micromanipulation operations, such as membrane electroporation and microinjection, to effect shape transformations of the membrane and create a series of interconnected compartments. size and geometry of the network can be chosen according to its desired function. Membrane composition is controlled mainly during the self-assembly step, whereas the interior contents of individual containers is defined through a sequence of microneedle injections. networks cannot be fabricated with other currently available methods of giant unilamellar vesicle preparation (large unilamellar vesicle fusion or electroformation). Described in detail are also three transport modes, which are suitable for moving water-soluble or membranebound small molecules, polymers, Dna, proteins and nanoparticles within the networks. the fabrication protocol requires ~90 min, provided all necessary preparations are made in advance. the transport studies require an additional 60-120 min, depending on the transport regime. 20,29 . Once a needle is inside a GUV, the bilayer tightly seals around the tip. The adhesion of the membrane is typically strong enough to allow the pulling of lipid material from the membrane, thereby instantly forming an open nanoconduit between the vesicle and the capillary. The flexible lipid nanotubes created in this way can be expanded at the needle-connected end by means of positive injection pressure, to an extent that a new vesicle is formed (Fig. 1, stage IV). Constant subsequent injection of fluid from the needle allows the 'daughter' vesicle to grow to a size appropriate for deposition onto the substrate (Fig. 1, stage V). Iteration of this pulling and vesiclegeneration process enables the building of whole networks of interconnected containers, in which size, geometry and individual contents can be controlled. If a new needle with different internal solution is used for the generation of each new vesicle, a network with differentiated contents can be created. The composition of the internal volume of each newly created vesicle is determined by the size ratio of mother and daughter vesicles 30 .As the nanoconduits are open on both ends and thus truly interconnect the individual containers, exchange of internal solution, and chemical compounds dissolved therein, is possible. Different regimes of exchange of matter have been investigated by us. In particular, the transport of small molecules and nanoparticles by diffusion [31][32][33] , by membrane tension-driven (Marangoni) flow 3...

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Section: Applications and Limitationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Generation of phospholipid vesicle-nanotube networks and transport of molecules therein

et al. 2011

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“…6,8,10,47,48 Previous theoretical studies provide insight into the stability of the tubular membrane protrusion following the disassembly of the inner rod cytoskeleton, 4 or into the stability of actin-free filopodia. 10,49 Accordingly, it is possible that the accumulation of cholesterol-sphingomyelin membrane nanodomains of anisotropic spontaneous curvature may contribute to the tube stability by overcoming the decrease in configurational entropy during the process of lateral sorting of the nanodomains.…”

Section: Discussionmentioning

confidence: 99%

“…10,49 Accordingly, it is possible that the accumulation of cholesterol-sphingomyelin membrane nanodomains of anisotropic spontaneous curvature may contribute to the tube stability by overcoming the decrease in configurational entropy during the process of lateral sorting of the nanodomains. 8,6,10,[48][49][50] Therefore, the loss of cholesterol-sphingomyelin rafts that may be connected to reduced intrinsic anisotropy of the tube membrane might cause dynamic instability leading to the retraction of disconnected ICNs.…”

Section: Discussionmentioning

confidence: 99%

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The role of cholesterol-sphingomyelin membrane nanodomains in the stability of intercellular membrane nanotubes

Lokar

Kabaso²,

Resnik³

et al. 2012

IJN

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Intercellular membrane nanotubes (ICNs) are highly curved tubular structures that connect neighboring cells. The stability of these structures depends on the inner cytoskeleton and the cell membrane composition. Yet, due to the difficulty in the extraction of ICNs, the cell membrane composition remains elusive. In the present study, a raft marker, ostreolysin, revealed the enrichment of cholesterol-sphingomyelin membrane nanodomains along ICNs in a T24 (malignant) urothelial cancer cell line. Cholesterol depletion, due to the addition of methyl-β-cyclodextrin, caused the dispersion of cholesterol-sphingomyelin membrane nanodomains and the retraction of ICNs. The depletion of cholesterol also led to cytoskeleton reorganization and to formation of actin stress fibers. Live cell imaging data revealed the possible functional coupling between the change from polygonal to spherical shape, cell separation, and the disconnection of ICNs. The ICN was modeled as an axisymmetric tubular structure, enabling us to investigate the effects of cholesterol content on the ICN curvature. The removal of cholesterol was predicted to reduce the positive spontaneous curvature of the remaining membrane components, increasing their curvature mismatch with the tube curvature. The mechanisms by which the increased curvature mismatch could contribute to the disconnection of ICNs are discussed.

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Ultrastructural characteristics of ovine bone marrow‐derived mesenchymal stromal cells cultured with a silicon stabilized tricalcium phosphate bioceramic

Desantis

Accogli

Burk

et al. 2017

Microscopy Res & Technique

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Bioceramics are being used in experimental bone engineering application in association with bone marrow derived mesenchymal stem cells (BM-MSCs) as a new therapeutic tool, but their effects on the ultrastructure of BM-MSCs are yet unknown. In this study we report the morphological features of ovine (o)BM-MSCs cultured with Skelite, a resorbable bioceramic based on silicon stabilized tricalcium phosphate (SiTCP), able to promote the repair of induced bone defect in sheep model. oBM-MSCs were isolated from the iliac crest, cultured until they reached near-confluence and incubated with SiTCP. After 48 hr the monolayers were highly damaged and only few cells adhered to the plastic. Thus, SiTCP was removed, and after washing the cells were cultured until they became confluent. Then, they were trypsinizated and processed for transmission electron microscopy (TEM) and RT-PCR analysis. RT-PCR displayed that oBM-MSCs express typical surface marker for MSCs. TEM revealed the presence of electron-lucent cells and electron-dense cells, both expressing the CD90 surface antigen. The prominent feature of electron-lucent cells was the concentration of cytoplasmic organelles around the nucleus as well as large surface blebs containing glycogen or profiles of endoplasmic reticulum. The dark cells had a multilocular appearance by the presence of peripheral vacuoles. Some dark cells contained endocytic vesicles, lysosomes, and glycogen aggregates. oBM-MSCs showed different types of specialized interconnections. The comparison with ultrastructural features of untreated oBM-MSCs suggests the light and dark cells are two distinct cell types which were differently affected by SiTCP bioceramic. Skelite cultured ovine BM-MSCs display electron-dense and electron-lucent cells which are differently affected by this bioceramic. This suggests that they could play a different role in bioceramic based therapy.

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Intercellular nanotubes: insights from imaging studies and beyond

Cited by 79 publications

References 108 publications

Generation of phospholipid vesicle-nanotube networks and transport of molecules therein

Generation of phospholipid vesicle-nanotube networks and transport of molecules therein

The role of cholesterol-sphingomyelin membrane nanodomains in the stability of intercellular membrane nanotubes

Ultrastructural characteristics of ovine bone marrow‐derived mesenchymal stromal cells cultured with a silicon stabilized tricalcium phosphate bioceramic

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