Trigger lipids inducing pH-dependent liposome fusion
Yoshikatsu Ogawa1, Masato Kodaka, Hiroaki Okuno
1Institute of Molecular and Cell Biology, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Center, AIST Tsukuba Center 6, 1-1-1 Higashi, Tsukuba, Ibaraki, Japan.
Chemistry and Physics of Lipids
|September 25, 2002
Summary
Aspartic acid-derived artificial lipids (ADLs) were synthesized to investigate liposome fusion. ADL6, ADL8, and ADL10 demonstrated significant lipid-mixing ability in acidic conditions, indicating their potential for membrane fusion applications.
Area of Science:
- Biochemistry
- Materials Science
- Chemical Engineering
Background:
- Liposome technology is crucial for drug delivery and biomimetic systems.
- Understanding membrane fusion mechanisms is key to controlling liposome behavior.
- Developing novel synthetic lipids can enhance liposome functionality.
Purpose of the Study:
- To design and synthesize novel aspartic acid-derived artificial lipids (ADLs).
- To investigate the ability of these ADLs to induce liposome fusion.
- To identify ADLs with optimal properties for membrane fusion.
Main Methods:
- Synthesis of ADLs with varying carboxyl alkyl chain lengths (s=2, 4, 6, 8, 10, 12).
- Incorporation of ADLs into liposome membranes via sonication.
- Fluorescence resonance energy transfer (FRET) measurements to assess lipid-mixing ability and membrane fusion.
Main Results:
- ADL6, ADL8, and ADL10 exhibited high lipid-mixing ability in acidic solutions.
- These specific ADLs effectively induced liposome fusion under acidic conditions.
- Other ADLs showed limited fusion activity at both acidic and neutral pH.
Conclusions:
- The hydrophobicity of head groups in ADL6, ADL8, and ADL10 is suitable for triggering membrane fusion.
- These ADLs represent promising candidates for applications requiring controlled liposome fusion.
- Tailored ADL structures can effectively modulate liposome membrane dynamics.
Related Concept Videos
01:38Receptor-mediated Endocytosis
Overview
01:26Membrane Fluidity
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
01:26Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:43SNAREs and Membrane Fusion
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
01:19Membrane Asymmetry Regulating Transporters
Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...