A post by Geiger group student Naomi Dalchand summarizing her new paper on polycation:lipid bilayer interactions in the Journal of Physical Chemistry C.

Eating a Sandwich in the Rain*

Imagine a roasted turkey sandwich, chock full of fresh, leafy greens and cut tomatoes strung together in a delightfully concise package, surrounded by two sheets of perfectly sliced bread. Without the bread, your sandwich would fall apart, the same way a biological cell would fall apart without its own exterior barrier, the cell membrane. Just as if you imagine walking outside eating your sandwich on a rainy day, the bread would provide protection for the filling. Sure, the bread would be a little soggy, but maybe you should think twice about walking outside in the rain without an umbrella! In a way, constructing a sandwich is like constructing a cell.

Like the various types of bread composing a sandwich, there are various differences between cell membranes and what they contain. Among the sesame-coated, honey-glazed, and pumpkin flavored options, the very classic white bread selection always rears its flavorless head. And why is it still an active contender for bread fanatics everywhere when there are so many other mouthwatering selections anyway? White bread is the safest and least complex of choices. Similarly, laboratory models for cell membranes possess a white bread option, supported lipid bilayers (SLBs), which are a useful, reliable, albeit simplistic, idealized model system for this exterior barrier. In fact, SLBs are what I use in my own research to study the toxicity of materials. And there you have it, white bread has risen as valuable once again!

As a less complex option, studying SLBs can help you understand initial interactions between materials and biological systems without the complication of proteins, receptors, and other components that can be found integrated on cell membranes. SLBs are extensively made of only lipids, fats such as those that make up the butter and oils found in your kitchen. As with the different selection of bread, there are different lipids that can be used to build SLBs. These lipids can differ in terms of chain length, charge, and degree of saturation. We can vary any of these parameters to tune important SLB properties and cater to the goal of testing scientific hypotheses in our experiments. My newly published work focuses on how water molecules above SLBs having different charges are impacted by varying concentrations of the common positively charged polymer, poly(allylamine hydrochloride) or PAH. Water encapsulates the cell and is important to its function, while changes to this environment can lead to improper cellular function and possible cell death. So yeah, a minor flaw in the sandwich analogy after all, bread in water not so good, cells in water, very good.

Polymers exist all around you and make up items such as plastic bags and balloons. On the topic of imagining food, you can also imagine the assembly of a polymer much like stringing popcorn together for your Christmas tree (did you know that 13 December is National Popcorn String Day? It’s really a thing!). Each popcorn piece embodies what is known as a monomer, a single unit. Linking several of these pieces together along a thin piece of thread gives you multiple monomers added together, termed a polymer. The polymer I used in my experiments, PAH, is positively charged. When it interacts with SLBs of opposite charge, we see that opposites do, in fact, attract! PAH is so inclined to interact with these negatively charged lipids that in doing so, the water molecules above the lipids are displaced. This is contrary to lipids that have a neutral or zwitterionic charge, in which only a small amount of water molecules are displaced. Not only does charge play a role in this interaction, but also the size of each particular lipid. Negatively charged lipids are much more condensed and therefore, pack together more closely to one another, only allowing for a small number of water molecules at the surface of the SLBs. Therefore, it requires much less PAH to displace water above a negatively charged SLB as opposed to the much larger, neutral lipids. Given that water as the “universal solvent” drives a lot of biological, physical, and chemical processes in living things, this insight is pretty important!

To study the water above our SLB’s we use a laser technique called sum frequency generation (SFG) spectroscopy. Although it would be eventful to blast villains with these laser beams, as most superheroes often do, I settle to direct them at my sample of SLBs to study their interactions with the positively charged polymers. If I must say so myself, the interaction of SLBs and polymers is just as important as saving the world: From this study we learn a lot more about the toxicity of polymers on living systems that had been known before on the molecular scale, which will ultimately help us design safer materials in consumer products, more efficient transfection agents for health-related applications, and perhaps even discover new chemistries for biologically recycling plastics. And science without fundamental experiments like these is …, well, let’s just say it’s like eating a sandwich in the rain with an umbrella: necessary!

*Images from https://drawception.com/game/1NZDDHptt2/sandwiches-everywhere/ and https://foodimentary.com/2018/12/13/december-13th-is-national-popcorn-string-day-4/