| Title |
Phase-Separated Liposomes Enhance the Efficiency of Macromolecular Delivery to the Cellular Cytoplasm
|
|---|---|
| Published in |
Cellular and Molecular Bioengineering, May 2017
|
| DOI | 10.1007/s12195-017-0489-4 |
| Pubmed ID | |
| Authors |
Zachary I. Imam, Laura E. Kenyon, Grant Ashby, Fatema Nagib, Morgan Mendicino, Chi Zhao, Avinash K. Gadok, Jeanne C. Stachowiak |
| Abstract |
From viruses to organelles, fusion of biological membranes is used by diverse biological systems to deliver macromolecules across membrane barriers. Membrane fusion is also a potentially efficient mechanism for the delivery of macromolecular therapeutics to the cellular cytoplasm. However, a key shortcoming of existing fusogenic liposomal systems is that they are inefficient, requiring a high concentration of fusion-promoting lipids in order to cross cellular membrane barriers. Toward addressing this limitation, our experiments explore the extent to which membrane fusion can be amplified by using the process of lipid membrane phase separation to concentrate fusion-promoting lipids within distinct regions of the membrane surface. We used confocal fluorescence microscopy to investigate the integration of fusion-promoting lipids into a ternary lipid membrane system that separated into liquid-ordered and liquid-disordered membrane phases. Additionally, we quantified the impact of membrane phase separation on the efficiency with which liposomes transferred lipids and encapsulated macromolecules to cells, using a combination of confocal fluorescence imaging and flow cytometry. Here we report that concentrating fusion-promoting lipids within phase-separated lipid domains on the surfaces of liposomes significantly increases the efficiency of liposome fusion with model membranes and cells. In particular, membrane phase separation enhanced the delivery of lipids and model macromolecules to the cytoplasm of tumor cells by at least 4-fold in comparison to homogenous liposomes. Our findings demonstrate that phase separation can enhance membrane fusion by locally concentrating fusion-promoting lipids on the surface of liposomes. This work represents the first application of lipid membrane phase separation in the design of biomaterials-based delivery systems. Additionally, these results lay the ground work for developing fusogenic liposomes that are triggered by physical and molecular cues associated with target cells. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 75% |
| Unknown | 1 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 25% |
| Members of the public | 1 | 25% |
| Practitioners (doctors, other healthcare professionals) | 1 | 25% |
| Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 48 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 11 | 23% |
| Student > Bachelor | 9 | 19% |
| Researcher | 7 | 15% |
| Student > Master | 3 | 6% |
| Professor | 1 | 2% |
| Other | 3 | 6% |
| Unknown | 14 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Materials Science | 7 | 15% |
| Biochemistry, Genetics and Molecular Biology | 7 | 15% |
| Engineering | 5 | 10% |
| Agricultural and Biological Sciences | 3 | 6% |
| Chemical Engineering | 3 | 6% |
| Other | 7 | 15% |
| Unknown | 16 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 October 2017.
All research outputs
#7,473,788
of 22,979,862 outputs
Outputs from Cellular and Molecular Bioengineering
#147
of 460 outputs
Outputs of similar age
#118,784
of 313,723 outputs
Outputs of similar age from Cellular and Molecular Bioengineering
#2
of 5 outputs
Altmetric has tracked 22,979,862 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 460 research outputs from this source. They receive a mean Attention Score of 3.2. This one has gotten more attention than average, scoring higher than 67% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 313,723 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.
We're also able to compare this research output to 5 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.