loading page

Kinetic Analysis of Cellular Internalization and Expulsion of Unstructured D-chirality Cell Penetrating Peptides
  • +5
  • Manibarathi Vaithiyanathan,
  • Hannah Hymel,
  • Nora Safa,
  • Olivia Sanchez,
  • Jacob Pettigrew,
  • Cole Kirkpatrick,
  • Ted Gauthier,
  • Adam Melvin
Manibarathi Vaithiyanathan
Louisiana State University System

Corresponding Author:[email protected]

Author Profile
Hannah Hymel
Louisiana State University System
Author Profile
Nora Safa
Louisiana State University System
Author Profile
Olivia Sanchez
Louisiana State University System
Author Profile
Jacob Pettigrew
Louisiana State University System
Author Profile
Cole Kirkpatrick
Louisiana State University System
Author Profile
Ted Gauthier
LSU Agricultural Center
Author Profile
Adam Melvin
Louisiana State University System
Author Profile


Most cell penetrating peptides (CPPs) are unstructured and susceptible to proteolytic degradation. One alternative is to incorporate D-chirality amino acids into unstructured CPPs to allow for enhanced uptake and intracellular stability. This work investigates CPP internalization using a series of time, concentration, temperature, and energy dependent studies, resulting in a three-fold increase in uptake and 50-fold increase in stability of D-chirality peptides over L-chirality counterparts. CPP internalization occurred via a combination of direct penetration and endocytosis, with a percentage of internalized CPP expelling from cells in a time-dependent manner. Mechanistic studies identified that cells exported the intact internalized D-chirality CPPs via an exocytosis independent pathway, analogous to a direct penetration method out of the cells. These findings highlight the potential of D-chirality CPPs as bio-vectors in therapeutic and biosensing applications, but also identify a new expulsion method suggesting a relationship between uptake kinetics, intracellular stability, and export kinetics
07 Apr 2020Submitted to AIChE Journal
14 Apr 2020Submission Checks Completed
14 Apr 2020Assigned to Editor
16 Apr 2020Reviewer(s) Assigned
18 May 2020Editorial Decision: Revise Major
19 Jun 20201st Revision Received
25 Jun 2020Assigned to Editor
25 Jun 2020Submission Checks Completed
26 Jun 2020Reviewer(s) Assigned
20 Jul 2020Editorial Decision: Revise Major
03 Sep 20202nd Revision Received
11 Sep 2020Submission Checks Completed
11 Sep 2020Assigned to Editor
14 Sep 2020Reviewer(s) Assigned
01 Oct 2020Editorial Decision: Accept