A nanoelectromechanosensing approach to detect cancerous transformation of single cells

(Nanowerk Spotlight) Future medical diagnostics will rely on nanotechnology-enabled sensors to detect changes in individual cells, for instance cell surface charge, to detect diseases at their earliest stage (see for instance: "Graphene-based optical sensor detects single cancer cells"). Since diseased cells, such as cancer cells, frequently carry information that distinguishes them from normal cells, accurate probing of these cells is critical for early detection of a disease.

Adding to these highly accurate methods for monitoring such alterations in single cells, researchers have now demonstrated a nanoelectromechanical procedure to relate the correlation between the mechanical stimulation of a cell's actin filaments and the electrical activities of ion channels to the cancerous state of the cell.

This is a novel modality in single-cell, label-free cancer grading based on electrical signal recording by silicon nanotube probes from mechanically aspirated normal and cancer cells by electrically activated borosilicate micropipette.

The team, led by professors Mohammad Abdolahad, Morteza Mahmoudi and Shams Mohajerzadeh from the University of Tehran, has reported their findings in the December 8, 2014 online edition of Nanoscale ("Single-cell correlative nanoelectromechanosensing approach to detect cancerous transformation: Monitoring the function of F-actin microfilaments in the modulation of ion channel activity").

The schematic shows the actin microfilament distribution for non-aspirated (left) and aspirated cells (right), respectively, in which the green lines represent actin microfilaments. (© Royal Society of Chemistry)

"In our investigation, the silicon nanotube (SiNT)-based electrical probes have been used as ultra-accurate signal recorders with subcellular resolution in order to electrically monitor cellular mechanosensing," Mahmoudi tells Nanowerk. "It should be noted that the introduced technology in this study may create numerous opportunities for fundamental biological research and applications. This novel probe could play a role as new cancer diagnostic methodology based on real-time correlations between mechanical and electrical behavior of single cells."

"Previous reports found that actin microfilaments can control the activity of ion channels in cell membrane," explains Abdolahad. "Our new method investigates the effect of mechanical stresses of actin filaments on electrical signals of cell membranes and finally relate such effects to a cancerous state of the cell. The actin of cancer cells are bundled and functionally disrupted (confirmed by confocal images presented in the paper)."

"We showed that the actin filaments of cancer cells are functionally disrupted so they couldnt respond to mechanical stimulation and they wouldnt affect the modulation of ion channels," adds Mohajerzadeh. "As a result, the electrical signals of aspirated cancer cell membranes wouldnt change in contrast to normal cells."

This current work is based on the team's recent achievements of fabricating silicon nanotubes ("A NickelGold Bilayer Catalyst Engineering Technique for Self-Assembled Growth of Highly Ordered Silicon Nanotubes (SiNT)") and single cell electrical recording by carbon nanotubes ("Single-cell resolution diagnosis of cancer cells by carbon nanotube electrical spectroscopy"), which has required them to more deeply explore the role of cells' cytoskeletal structure – such as actin and microtubules – in generating electrical signatures of cancerous transformation.

The results have opened a new window in the field of cancer nanoelectromechanosensing and some hidden relations between cells organelles with mechanical and electrical roles in cancerous transformation

"Our newly introduced methodology allowed us to diagnose cancerous transformation at single-cell resolution by a label-free nanoelectromechanical approach," says Mahmoudi. "Additionally, this application could improve early detection of cancer which improves treatment efficacy of diseases in the clinical stage."