PhD Scientific Days 2021

TT_II_P: Theoretical and Translational Medicine II. Posters

Photosensitization induced membrane disruption studied with Atomic Force Microscopy

Text of the abstract

Introduction:
Photosensitization is a treatment modality that is made into the first-line treatment as well. The basis of the treatment is that a dye usually a porphyrin derivative is irradiated, which leads to the formation of reactive oxygen species (ROS). The limited lifetime of the generated ROS confines the bulk of the harmful alterations of cell components in the region where the photosensitizer is accumulated inside the cells. Most Photosensitizers are preferably located in the membrane environment compared to the hydrophilic environment of the cytosol. The membrane environment mostly consists of phospholipids the study of photo-induced damage to membrane lipids can greatly increase the understanding of ROS-induced membrane disruption in pathological and therapeutical conditions.
Aims:
The Topographical and nanomechanical characterization of the ROS-induced membrane changes.
Methods:
To determine the topography of the supported lipid bilayers we mapped the surface with non-contact mode AFM imaging. Force spectroscopy measurements were carried out on the samples to determine the ROS-induced nanomechanical shifts in our model.
Results:
The AFM images of DPPC-DOPC membranes displayed structural changes due to irradiation. The membrane integrity was disrupted nanoscopic pores were detectable. To investigate the underlying mechanism behind the permeabilization the force spectroscopy measurements were carried out. Membrane rupture forces are a mechanical fingerprint of membranes assessable with force spectroscopy, which shifted with irradiation. These phenomenons did not occur in the control sample, which only consisted of DPPC as the membranes of fully saturated lipids were not perturbed with the performed influence.
Conclusion:
Photoinduced membrane disruption leads to membrane nanopore formation and nanomechanical alterations in bilayers containing unsaturated membrane constituents.
Funding:
The study was supported by EFOP-3.6.3-VEKOP-16-2017-00009 of the National Research, Development, and Innovation Office, Hungary.
The research was financed by the Higher Education Institutional Excellence Programme of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development thematic program of the Semmelweis University.

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences