scholarly journals Key Process and Factors Controlling the Direct Translocation of Cell-Penetrating Peptide through Bio-Membrane

2020 ◽  
Vol 21 (15) ◽  
pp. 5466 ◽  
Author(s):  
Kazutami Sakamoto ◽  
Taku Morishita ◽  
Kenichi Aburai ◽  
Kenichi Sakai ◽  
Masahiko Abe ◽  
...  
Keyword(s):  
Time Course ◽  
Phase Transfer ◽  
Membrane Lipid ◽  
Cell Penetrating Peptide ◽  
Giant Unilamellar Vesicle ◽  
Dynamic Membrane ◽  
Chemical Mediator ◽  
Lipid Molecule ◽  
Cell Penetrating ◽  
Lipid Adsorption

Cell-penetrating peptide (CPP) can directly penetrate the cytosol (cytolysis) and is expected to be a potent vector for a drug delivery system (DDS). Although there is general agreement that CPP cytolysis is related to dynamic membrane deformation, a distinctive process has yet to be established. Here, we report the key process and factors controlling CPP cytolysis. To elucidate the task, we have introduced trypsin digestion of adsorbed CPP onto giant unilamellar vesicle (GUV) to quantify the adsorption and internalization (cytolysis) separately. Also, the time-course analysis was introduced for the geometric calculation of adsorption and internalization amount per lipid molecule consisting of GUV. As a result, we found that adsorption and internalization assumed to occur successively by CPP molecule come into contact with membrane lipid. Adsorption is quick to saturate within 10 min, while cytolysis of each CPP on the membrane follows successively. After adsorption is saturated, cytolysis proceeds further linearly by time with a different rate constant that is dependent on the osmotic pressure. We also found that temperature and lipid composition influence cytolysis by modulating lipid mobility. The electrolyte in the outer media is also affected as a chemical mediator to control CPP cytolysis by following the Hoffmeister effect for membrane hydration. These results confirmed the mechanism of cytolysis as temporal and local phase transfer of membrane lipid from Lα to Mesh1, which has punctured bilayer morphologies.

scholarly journals Direct entry of cell-penetrating peptide can be controlled by maneuvering the membrane curvature

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kazutami Sakamoto ◽  
Taku Morishita ◽  
Kenichi Aburai ◽  
Daisuke Ito ◽  
Tomohiro Imura ◽  
...  
Keyword(s):  
Phase Transfer ◽  
Cell Model ◽  
Membrane Curvature ◽  
Conclusive Evidence ◽  
Water Soluble ◽  
Cell Penetrating Peptide ◽  
Local Dynamic ◽  
Functional Flexibility ◽  
Single Cell Model ◽  
Cell Penetrating

AbstractA biomembrane's role is to be a barrier for interior cytosol from an exterior environment to execute the cell's normal biological functions. However, a water-soluble peptide called cell-penetrating peptide (CPP) has been known for its ability to directly penetrate through the biomembranes into cells (cytolysis) without perturbating cell viability and expected to be a promising drug delivery vector. Examples of CPP include peptides with multiple arginine units with strong cationic properties, which is the key to cytolysis. Here we show the conclusive evidence to support the mechanism of CPP’s cytolysis and way to control it. The mechanism we proposed is attributed to biomembrane’s physicochemical nature as lamellar liquid crystal (Lα). Cytolysis occurs as the temporal and local dynamic phase transitions from Lα to an undulated lamellar with pores called Mesh1. We have shown this phase transfer of Lα composed of dioleoyl-phosphatidylcholine (DOPC) with water by adding oligo-arginine (Rx) as CPP at the equilibrium. Using giant unilamellar vesicle composed of DOPC as a single cell model, we could control the level of cytolysis of CPP (FITC-R8) by changing the curvature of the membrane through osmotic pressure modulation. The cytolysis of CPP utilizes biomembrane's inherent topological and functional flexibility corresponding to the stimuli.

scholarly journals Effect of Vesicle Size on the Cytolysis of Cell-Penetrating Peptides (CPPs)

2020 ◽  
Vol 21 (19) ◽  
pp. 7405
Author(s):  
Kazutami Sakamoto ◽  
Takeshi Kitano ◽  
Haruka Kuwahara ◽  
Megumi Tedani ◽  
Kenichi Aburai ◽  
...  
Keyword(s):  
Phase Transfer ◽  
Membrane Lipids ◽  
Positive Curvature ◽  
Membrane Lipid ◽  
Cell Penetrating Peptides ◽  
Membrane Curvature ◽  
Local Phase ◽  
Vesicle Size ◽  
Cell Penetrating ◽  
A Cell

A specific series of peptides, called a cell-penetrating peptide (CPP), is known to be free to directly permeate through cell membranes into the cytosol (cytolysis); hence, this CPP would be a potent carrier for a drug delivery system (DDS). Previously, we proposed the mechanism of cytolysis as a temporal and local phase transfer of membrane lipid caused by positive membrane curvature generation. Moreover, we showed how to control the CPP cytolysis. Here, we investigate the phospholipid vesicle’s size effect on CPP cytolysis because this is the most straightforward way to control membrane curvature. Contrary to our expectation, we found that the smaller the vesicle diameter (meaning a higher membrane curvature), the more cytolysis was suppressed. Such controversial findings led us to seek the reason for the unexpected results, and we ended up finding out that the mobility of membrane lipids as a liquid crystal is the key to cytolysis. As a result, we could explain the cause of cytolysis suppression by reducing the vesicle size (because of the restriction of lipid mobility); osmotic pressure reduction to enhance positive curvature generation works as long as the membrane is mobile enough to modulate the local structure. Taking all the revealed vital factors and their effects as a tool, we will further explore how to control CPP cytolysis for developing a DDS system combined with appropriate cargo selection to be tagged with CPPs.

scholarly journals Designed Cell-Penetrating Peptide Inhibitors of Amyloid-beta Aggregation and Cytotoxicity

2020 ◽  
Vol 1 (2) ◽  
pp. 100014 ◽  
Author(s):  
Anja Henning-Knechtel ◽  
Sunil Kumar ◽  
Cecilia Wallin ◽  
Sylwia Król ◽  
Sebastian K.T.S. Wärmländer ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Peptide Inhibitors ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

18F-Labeled phosphopeptide-cell-penetrating peptide dimers with enhanced cell uptake properties in human cancer cells

2012 ◽  
Vol 39 (8) ◽  
pp. 1202-1212 ◽  
Author(s):  
Susan Richter ◽  
Vincent Bouvet ◽  
Melinda Wuest ◽  
Ralf Bergmann ◽  
Joerg Steinbach ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Cell Uptake ◽  
Cell Penetrating Peptide ◽  
Human Cancer Cells ◽  
Cell Penetrating

scholarly journals Identification of a new cell-penetrating peptide derived from the african swine fever virus CD2v protein

Drug Delivery ◽  
2021 ◽  
Vol 28 (1) ◽  
pp. 957-962
Author(s):  
Shunli Yang ◽  
Xinming Zhang ◽  
Yuying Cao ◽  
Shuo Li ◽  
Junjun Shao ◽  
...  
Keyword(s):  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

Enhanced oral absorption of insulin using colon-specific nanoparticles co-modified with amphiphilic chitosan derivatives and cell-penetrating peptides

2019 ◽  
Vol 7 (4) ◽  
pp. 1493-1506 ◽  
Author(s):  
Feng Guo ◽  
Ting Ouyang ◽  
Taoxing Peng ◽  
Xiuying Zhang ◽  
Baogang Xie ◽  
...  
Keyword(s):  
Oral Absorption ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Chitosan Derivative ◽  
Chitosan Derivatives ◽  
Cell Penetrating

In this study, amphipathic chitosan derivative (ACS) and cell-penetrating peptide (CPP) co-modified colon-specific nanoparticles (CS-CPP NPs) were prepared and evaluated.

Sign in / Sign up

Export Citation Format

Share Document