Transmembrane transport of Multicomponent Liposome-Nanoparticles into Giant Vesicles

Abstract Background Pathological remodeling of the myocardium has long been known to involve oxidant signaling, but so far, strategies using systemic anti-oxidants have generally failed to prevent it. Aquaporins are a family of transmembrane water channels with thirteen isoforms currently known. Some isoforms have been implicated in oxidant signaling. AQP1 is the most abundant aquaporin in cardiovascular tissues but its specific role in cardiac remodeling remains unknown. Purpose We tested the role of AQP1 as a key regulator of oxidant-mediated cardiac remodeling amenable to targeted pharmacological therapy. Methods We used mice with genetic deletion of Aqp1 (and wild-type littermate), as well as primary isolates from the same mice and human iPSC/Engineered Heart Tissue to test the role of AQP1 in pro-hypertrophic signaling. Human cardiac myocyte-specific (PCM1+) expression of AQP's and genes involved in hypertrophic remodeling was studied by RNAseq and bioinformatic GO pathway analysis. Results RNA sequencing from human cardiac myocytes revealed that the archetypal AQP1 is a major isoform. AQP1 expression correlates with the severity of hypertrophic remodeling in patients with aortic stenosis. The AQP1 channel was detected at the plasma membrane of human and mouse cardiac myocytes from hypertrophic hearts, where it colocalizes with the NADPH oxidase-2 (NOX2) and caveolin-3. We show that hydrogen peroxide (H2O2), produced extracellularly, is necessary for the hypertrophic response of isolated cardiac myocytes and that AQP1 facilitates the transmembrane transport of H2O2 through its water pore, resulting in activation of oxidant-sensitive kinases in cardiac myocytes. Structural analysis of the amino acid residues lining the water pore of AQP1 supports its permeation by H2O2. Deletion of Aqp1 or selective blockade of AQP1 intra-subunit pore (with Bacopaside II) inhibits H2O2 transport in mouse and human cells and rescues the myocyte hypertrophy in human induced pluripotent stem cell-derived engineered heart muscle. This protective effect is due to loss of transmembrane transport of H2O2, but not water, through the intra-subunit pore of AQP1. Treatment of mice with clinically-approved Bacopaside extract (CDRI08) inhibitor of AQP1 attenuates cardiac hypertrophy and fibrosis. Conclusion We provide the first demonstration that AQP1 functions as an aqua-peroxiporin in primary rodent and human cardiac parenchymal cells. We show that cardiac hypertrophy is mediated by the transmembrane transport of H2O2 through the AQP1 water channel. Our studies open the way to complement the therapeutic armamentarium with specific blockers of AQP1 for the prevention of adverse remodeling in many cardiovascular diseases leading to heart failure. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): FRS-FNRS, Welbio

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pH-Tolerant giant vesicles composed of cationic lipids with imine linkages and oleic acids

RSC Advances ◽

10.1039/d0ra06822e ◽

2020 ◽

Vol 10 (56) ◽

pp. 34247-34253

Author(s):

Daichi Sawada ◽

Ayana Hirono ◽

Kouichi Asakura ◽

Taisuke Banno

Keyword(s):

Oleic Acid ◽

Cationic Lipids ◽

Giant Vesicles ◽

Acidic Conditions

Giant vesicles composed of cationic lipids having an imine linkage and oleic acid were stable at strong acidic conditions.

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Giant Vesicles Produced with Phosphatidylcholines (PCs) and Phosphatidylethanolamines (PEs) by Water-in-Oil Inverted Emulsions

Life ◽

10.3390/life11030223 ◽

2021 ◽

Vol 11 (3) ◽

pp. 223

Author(s):

Boying Xu ◽

Jinquan Ding ◽

Jian Xu ◽

Tetsuya Yomo

Keyword(s):

Encapsulation Efficiency ◽

Analytical Study ◽

Giant Vesicles ◽

Imaging Flow Cytometry ◽

Artificial Cell ◽

Transfer Method ◽

Long Term Preservation ◽

Natural Cell ◽

Cell Construction

(1) Background: giant vesicles (GVs) are widely employed as models for studying physicochemical properties of bio-membranes and artificial cell construction due to their similarities to natural cell membranes. Considering the critical roles of GVs, various methods have been developed to prepare them. Notably, the water-in-oil (w/o) inverted emulsion-transfer method is reported to be the most promising, owning to the relatively higher productivity and better encapsulation efficiency of biomolecules. Previously, we successfully established an improved approach to acquire detailed information of 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)-derived GVs with imaging flow cytometry (IFC); (2) Methods: we prepared GVs with different lipid compositions, including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and PC/PE mixtures by w/o inverted emulsion methods. We comprehensively compared the yield, purity, size, and encapsulation efficiency of the resulting vesicles; (3) Results: the relatively higher productivities of GVs could be obtained from POPC, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE), DOPC: DLPE (7:3), and POPC: DLPE (6:4) pools. Furthermore, we also demonstrate that these GVs are stable during long term preservation in 4 °C. (4) Conclusions: our results will be useful for the analytical study of GVs and GV-based applications.

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Spontaneous Formation of Giant Phospholipid Vesicles

Zeitschrift für Naturforschung C ◽

10.1515/znc-1988-11-1222 ◽

1988 ◽

Vol 43 (11-12) ◽

pp. 938-947 ◽

Cited By ~ 2

Author(s):

Rolf-M. Servuss

Keyword(s):

Aqueous Solution ◽

Light Microscopy ◽

Fluid Phase ◽

Significant Part ◽

Phospholipid Vesicles ◽

Electrostatic Repulsion ◽

Giant Vesicles ◽

Spontaneous Formation

The spontaneous formation of giant (diameter > 10 μm) vesicles from a number of phospholipids in excess aqueous solution has been studied by light-microscopy. Electrically neutral as well as charged phospholipids swell to form giant vesicles only if the lipids are in the fluid phase. This shows that electrostatic repulsion alone cannot explain the spontaneous formation of giant vesicles. The results confirm the suggestion that steric forces between extended membranes play a significant part in this process.

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Photochemically induced cyclic morphological dynamics via degradation of autonomously produced, self-assembled polymer vesicles

Communications Chemistry ◽

10.1038/s42004-021-00464-8 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Chenyu Lin ◽

Sai Krishna Katla ◽

Juan Pérez-Mercader

Keyword(s):

Morphological Evolution ◽

Chemical Degradation ◽

Chemical Mechanism ◽

Giant Vesicles ◽

Water Influx ◽

Physico Chemical ◽

Osmotic Water ◽

Periodic Growth ◽

Oxygen Conditions ◽

Self Assembled

AbstractAutonomous and out-of-equilibrium vesicles synthesised from small molecules in a homogeneous aqueous medium are an emerging class of dynamically self-assembled systems with considerable potential for engineering natural life mimics. Here we report on the physico-chemical mechanism behind a dynamic morphological evolution process through which self-assembled polymeric structures autonomously booted from a homogeneous mixture, evolve from micelles to giant vesicles accompanied by periodic growth and implosion cycles when exposed to oxygen under light irradiation. The system however formed nano-objects or gelation under poor oxygen conditions or when heated. We determined the cause to be photoinduced chemical degradation within hydrated polymer cores inducing osmotic water influx and the subsequent morphological dynamics. The process also led to an increase in the population of polymeric objects through system self-replication. This study offers a new path toward the design of chemically self-assembled systems and their potential application in autonomous material artificial simulation of living systems.

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Electroformation of Giant Vesicles on a Polymer Mesh

Membranes ◽

10.3390/membranes1030184 ◽

2011 ◽

Vol 1 (3) ◽

pp. 184-194 ◽

Cited By ~ 6

Author(s):

Yukihisa Okumura ◽

Takuya Sugiyama

Keyword(s):

Giant Vesicles

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Myocardial CO2 buffering: role of transmembrane transport of H+ or HCO3-ions

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1976.230.4.1037 ◽

1976 ◽

Vol 230 (4) ◽

pp. 1037-1041 ◽

Cited By ~ 11

Author(s):

DR Strome ◽

RL Clancy ◽

NC Gonzalez

Keyword(s):

Small Volume ◽

Coronary Circulation ◽

Myocardial Cell ◽

Ringer Solution ◽

Red Cells ◽

Transmembrane Transport ◽

High Degree

Isolated rabbit hearts were perfused with rabbit red cells suspended in Ringer solution. A small volume of perfusate was recirculated for 10 min at Pco2 of 33.4 +/- 0.9 or 150.8 +/- 7.5 mmHg. Hypercapnia resulted in an increase in perfusate HCO3- concentration that was smaller than that observed when isolated perfusate was equilibrated in vitro with the same CO2 tensions (delta HCO-3e = 1.6 mM, P less than 0.01). This difference is consistent with a net movement of HCO3- into or H+ out of the mycardial cell, and cannot be accounted for by dilution of HCO3- in the myocardial interstitium. Recirculation of perfusate through the coronary circulation at normal Pco2 for two consecutive 10-min periods was not followed by changes in perfusate HCO3- concentration. A high degree of correlation (r = 0.81) was observed between intracellular HCO-3e concentration and the corresponding delta HCO-3e in individual experiments. The results suggest that transmembrane exchange of H+ or HCO3- is a buffer mechanism for CO2 in the myocardial cell.

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