One of the current paradigms of molecular biology research is to study cells by manipulating them. Insert a piece of DNA and see what changes. Add a protein and see if the cell can now become cancerous. Inactivate a protein and see if a diseased cell becomes normal.
One of the trickiest steps in such processes is often getting the foreign substance inside a cell. Living cells have membranes designed to keep out foreign substances and to absorb just what the cell wants. How do we let particularly large molecules in?
Infiltrating the Cell’s Walls
Pieces of DNA are usually inserted into a longer fragment of DNA called a vector (to keep the DNA stable). The cell is then shocked to jolt the proteins in its membrane and make it temporarily porous. This method can work for small molecules, and another method is the chemical disruption of the membrane temporarily. The problem with these methods is that they change some properties of the cell, and the goal of such experiments is to observe changes in the cell that is ONLY because of the inserted molecule, and not due to other factors (such that the result of a shock might lead to). Another method is to deliver the molecule inside nanoparticles which can then enter the cell, but the nanoparticle is often captured by an organelle of the cell, and the molecule is then not released. The cell’s membrane also allows certain protein to pass through it—think of it like a gatekeeper, letting proteins of certain charges and small enough sizes go through while keeping out the others.
Squeezing Cells to Make Them Yield
A general method of insertion would thus be a useful tool in research. Researchers at MIT have come up with the solution mothers use when their children don’t eat food—they press in the child’s cheeks till their mouths open. This team has developed a microfluidics device that does something similar. Cells (and the delivery material) flow through a tubes under external pressure and are forced to pass through a tiny constriction in the tube (see figure). During this phase, the cells are compressed to such tiny sizes that their membranes ‘split’ temporarily, leaving gaps for molecules to enter.
The team used this method to generate stem cells (by inserting the necessary factors into cells) and found that this method had an efficiency 10 to 100 times greater than other existing methods. Their next step is to use this for therapeutic purposes, wherein a patient’s cells could be taken out of his body, injected with the necessary DNA/protein, and re-injected into his/her body.
You can read about this research here.