A promising candidate for treating incurable diseases is to reprogram the cells using relatively large biological molecules. However, since the reprogramming must take place inside the cell the pharmaceutical must penetrate the cell membrane. Designing and encapsulating biological molecules so that they are capable of this is very challenging.
The present research on improving how pharmaceuticals could be transported into the cell is based on fabricating nanoparticles, mimicking naturally occurring processes in the human body. Cells can, for instance, communicate by exchange of nano capsids. Furthermore, it is well known that viruses can penetrate the cell membrane and cause diseases such as gastric influenza, influenza, HIV and Zika. That healthy cells communicate via biological nanoparticles in a similar manner, however, is less well known.
Viruses binding to the surface of the cell utilize different entry mechanisms to gain entrance to the interior of the cell and deliver their genetic code. However, using viruses to get access to the same entrance mechanisms to instead deliver pharmaceuticals is risky. A safer route could be to utilize the mechanisms used for cell-to-cell communication via biological nanoparticles, according to Professor Fredrik Höök at the Department of Physics at Chalmers.
The new innovation makes it possible to characterize biological nanoparticles in a more sophisticated way. Previously, two separate methods were required to determine size and content and they were mutually exclusive; either the size or the content of a nanoparticle could be determined – not both. With the new method it is possible to simultaneously determine both size and content of a single nanoparticle.
– Since uptake of this new class of so called biological pharmaceuticals is dependent on both size and content of the nanoparticles, our innovation will hopefully yield better formulations of new pharmaceuticals. This kind of pharmaceuticals are not artificially made molecules, but rather made from biological molecules like DNA and RNA – the code that is the foundation for how cells work, says Fredrik Höök.
Together with two colleagues he is managing a company that owns the patent for the new innovation. In the same company there is also an earlier innovation enabling detection of biological nanoparticles without using so called fluorescent probes. The company, started by financial support from Vinnova and Swedish Foundation for Strategic Research (SFF), also collaborates with AstraZeneca and Sahlgrenska University Hospital. The new innovation has also been verified in collaboration with a group of researchers in Singapore.
The discovery of the new method was an unexpected stroke of luck.
– Two of my students, Stephan Block and Björn Fast, came to the realization that the problem should be solvable by thinking orthogonally. The moment when it worked was fantastic, with all the pieces of the puzzle suddenly finding their position, says Fredrik Höök.
Text: Mia Halleröd Palmgren
How it works
The concept utilizes the two-dimensional fluidity of an artificial cell membrane, a so-called lipid membrane. A biological nanoparticle bound to such a lipid membrane will perform a random movement across the surface, similar to the random movement it would have performed when free in solution.
There are, however, two crucial differences: Firstly, the movement is spatially limited to the plane of the lipid membrane; secondly the random movement is no longer determined by the size of the nanoparticle, but instead by the properties of the linker molecule in the membrane. If a hydrodynamic flow is applied along the surface, the nanoparticles start to move parallel to the flow. The larger the nanoparticle, the larger the force acting on it and the faster it will move. The velocity of the nanoparticle is linked to the applied force via the lipid membrane friction and to deduce the force acting on a nanoparticle, this membrane friction must thus be determined. Fortunately - and this is the crux of the invention - since the membrane friction is a function of the drag experienced when linked to the membrane, it can be deduced from the random movement of the nanoparticles. Knowing both the membrane friction and the nanoparticle’s velocity it is possible to calculate the force acting on the nanoparticle and from the force, the size is easy to determine.
Furthermore, since the movement of the nanoparticles is restricted to the two-dimensional surface of the membrane, they are in the focal plane at all times, enabling microscopic determination of their molecular content. Hence, it is possible to simultaneously determine both the size and the content of a nanoparticle.