期刊
出版社
ELSEVIER
DOI: 10.1016/j.msec.2020.111813
关键词
Layer-by-layer; Liposomes; Glycosaminoglycans; Supported vesicle layers; Extracellular matrix; Cell communication
资金
- Programa Iacobus
- Portuguese Fundacao para a Ciencia e a Tecnologia [PTDC/BTM-MAT/28327/2017, CEE-CIND/02842/2017, SFRH/BD/114847/2016]
- European Commission [ELASTISLET NMP-2014-646075, FORECAST 668983]
- Spanish AEI
- European Regional Development Fund [MAT2016-80266-R]
- Ministerio de Economia y Competitividad of Spain [MAT2016-80266-R]
- Xunta de Galicia (Grupo de Referencia Competitiva) [ED431C 2018/26]
- Xunta de Galicia (Agrupacion Estrategica de Materiales-AEMAT) [ED431E 2018/08]
- Fundação para a Ciência e a Tecnologia [PTDC/BTM-MAT/28327/2017, SFRH/BD/114847/2016] Funding Source: FCT
This study developed a simplified model to mimic EVs and their interactions with cells and the extracellular matrix by integrating various components, including poly-L-lysine, hyaluronic acid, liposomes, and Nile Red. The model was validated to effectively simulate the interactions between EVs and cells, showcasing the potential of using this model for further studies on EV/cell interactions.
Extracellular vesicles (EVs) are particles originating from the exfoliation of the cellular membrane. They are involved in cell-to-cell and cell-to-matrix signaling, exchange of bioactive molecules, tumorigenesis and metastasis, among others. To mitigate the limited understanding of EVs transfer phenomena, we developed a simplistic model that mimics EVs and their interactions with cells and the extracellular matrix. The proposed model is a layer by layer (LbL) film built from the polycationic poly-L-lysine (PLL) and the glycosaminoglycan hyaluronic acid (HA) to provide ECM mimicry. Positively charged 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and N-1 ,N-1 ,N-14 ,N-14-tetramethyl-N-1,N-14 -ditetradecyltetradecane-1,14-diaminium dibromide (GS14) liposomes were embedded in this construct to act as EVs analogs. To simulate EVs carrying substances, Nile Red was loaded as a model of lipophilic cargo molecules. The integration of each component was followed by quartz crystal microbalance measurements, which confirmed the immobilization of intact liposomes on the underlying (PLL/HA)(3) soft film. The release of Nile Red from liposomes either embedded in the LbL construct or exposed at its surface revealed a fast first order release. This system was validated as a model for EV/cell interactions by incubation with breast cancer cells MDA-MB-231. We observed higher internalization for embedded liposomes when compared with surface-exposed ones, showcasing that the ECM mimic layers do not constitute a barrier to liposome/cell interactions but favor them.
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