It’s a dust particle, it’s an anomaly, it’s. . .a particle aggregate?
I’ve noticed, as I ask people about their research, that I will most likely neither remember nor understand what they are saying unless I whip out my legal pad and pen to take notes. Therefore, I am presenting my research project in a different way, in hopes that it entertains you, and that you may even remember it, even if you don’t give a monkey’s uncle about particle aggregates.
Imagine you’re a heparin molecule. You’re not too big (about 70 kDa), you’re a sulfated protein chain and a pretty negative character (negatively charged that is, because of the sulfate groups). You are prescribed by doctors (via an intravenous sodium solution) to patients, since you serve as a blood thinner (the mechanism of how that works is irrelevant). So, you travel from your bottle, through a tube, into a vein, and thus you’re in the blood stream. You pass all sort of strange characters from erythrocytes to leukocytes, and even platelets. Speaking of platelets, they release a positively charged protein – platelet factor 4 (PF4). Love at first site, after all, you’re a negatively charged protein, and opposites attract. A complex is formed (between you and the PF4)! You continue your tour of the blood stream with your newfound traveling companion. The happy-go-lucky adventure becomes a nightmare when you find yourself being attacked by antibodies! The patient you are in is essentially having an allergic reaction (autoimmune response specifically) to you indirectly (more specifically it’s to the complex and not heparin alone). This is known as Heparin-induced Thrombocytopenia (HIT), with thrombocytopenia being a low platelet count.
This is where my lab and I come in. We’re investigating the immune response of HIT, because it is not fully understood. And not everyone that receives heparin injections develops the condition. The piece of the puzzle I am involved with involves complex formation and other aggregates. I’m looking at how you (heparin) and your cousins (other heparin molecules) bind to other positively-charged proteins (lysozyme and protamine). Do complexes form? How big, and in what molar ratios? How similar are they to the PF4/heparin complexes (which are the underlying principle of HIT).
Answering these questions or developing new questions from my experiment is just one more step toward ensuring your safe travels in blood :o)
