Cluster of Excellence –
University of Freiburg

Stiffness matters

Nanomedicine entry into cancer cells can be tuned by modulating the stiffness of the plasma membrane
Graphic: Prasad Shastri, Shengnan Xiang

Nanomedicines need to get taken up by diseased cells in order to release their cargo. Cancer cells have altered membrane properties, which hamper their ability to take up nanomedicines.  A research team led by Prof. Dr. Prasad Shastri at the University of Freiburg has shown that, the stiffness of cancer cell plasma membrane affects how nanoparticles get internalized, and this process can be enhanced when the cell plasma membrane stiffness is increased.  These findings are published in the scientific journal Small. 

“In order to increase therapeutic effectiveness, it is critical to find general principles that can positively influence uptake of nanomedicines into cells” emphasizes Shastri. A cell swallows nanomaterial from its immediate environment via deformation of the cell membrane through a process called endocytosis.  According to Shastri, up to this point research efforts have primarily focused on how and which membrane proteins are responsible for this process. It is still relatively unclear what role the biophysical properties of cell membrane play in this process.

The Freiburg team of Shastri, Dr. Shengnan Xiang and Dr. Melika Sarem, have now discovered that liposomes – nanoscale vesicles of lipid molecules encompassing an aqueous core – can be used to alter the stiffness of the cell plasma membrane through lipid transfer. Increasing the stiffness of cancer cell membrane enhanced the entry of polymer nanoparticles through pathways rich in cholesterol. “The results show that the biophysical properties of the cell membrane provide important starting points for further improving targeted treatment of tumor cells," summarizes Shastri.

Prasad Shastri is the Professor of Biofunctional Macromolecular Chemistry at the Institute for Macromolecular Chemistry and the Professor of Cell Signalling Environments in the Cluster of Excellence BIOSS Centre for Biological Signalling Studies at the University of Freiburg.

 

Original publication:

Liposomal treatment of cancer cells modulates uptake pathway of polymeric nanoparticles by altering membrane stiffness.
Xiang S, Sarem M, Shah S, Shastri VP.
Small. 2018 Feb 20. [Epub ahead of print]

http://onlinelibrary.wiley.com/doi/10.1002/smll.201704245/abstract;jsessionid=21B434F4D41B84C6837B5B7C83791DCB.f04t02