Ever left lettuce in the freezer by accident? When you thaw it out, instead of crisp leaves you get limp mush. That's because when water freezes, it expands into ice crystals that act like microscopic knives, slicing through cell membranes. Now imagine that same problem, but with something as complex as a human heart. You might think "well, that's why we have freezers that go colder - surely at some temperature it would freeze so fast the ice crystals wouldn't form?"
Dr. Yoed Rabin at Carnegie Mellon's Biothermal Technology Laboratory brings a mechanical engineer's perspective to what happens when tissues get cooled to ultra-low temperatures. But why would we need a mechanical engineer for a biological problem? As part of ATP-Bio (a multi-institution research center tackling biological preservation), Rabin works to reveal the invisible forces that can silently fracture vitrified organs during cooling and warming. His 2023 paper on thermomechanical stress in heart models, co-authored with Purva Joshi, highlights a problem at the intersection of materials science and biology.
So preventing ice crystals is step one in preservation. But what happens next? This is where Rabin's mechanical engineering background comes in handy. When biological tissue is transformed into something that behaves more like glass than ice, it enters unfamiliar territory. Extreme temperature changes create powerful forces that can tear materials apart from the inside.
This glass-like state is key to understanding both the promise and challenge of organ preservation. You probably know that glass is a solid, but it's a weird kind of solid. Unlike ice, which has a regular crystal structure, glass is what physicists call an amorphous solid - its molecules are locked in place but in a random arrangement, like a liquid that somehow froze without crystallizing. That's exactly what scientists are trying to achieve with organ preservation.
To do this, they first saturate the tissue with special solutions called cryoprotectants. One example is VS55, a carefully balanced mixture of chemicals including dimethyl sulfoxide (DMSO), propylene glycol, and formamide. While newer cryoprotectants exist, VS55 is particularly interesting because scientists have mapped out exactly how it behaves at every temperature - making it useful for understanding the fundamental physics of preservation.
You might think that preventing ice formation is enough - after all, isn't that what damages cells in the first place? But molecules are trickier than that. Even without forming ice, they can still move around and participate in chemical reactions that slowly degrade tissue. You know how honey gets sluggish in your kitchen cabinet when it’s cold? The colder it gets, the slower it flows. Now imagine cooling something until the molecules move so slowly that they practically stop altogether.
That's exactly what happens at what physicists call the glass transition temperature (Tg). For VS55, this occurs at -123°C. At this point, the molecules become so sluggish that the tissue enters an amorphous solid state - like honey that's become so thick it would take years to flow at all. This transformation alters the physical properties of the tissue. What was once flexible living matter becomes increasingly brittle and glass-like, changing how it responds to mechanical forces. Hearts that once beat rhythmically transform into structures that could fracture under thermal stress if not properly managed.
But wait, if -123°C stops molecular motion, why do preservation protocols call for cooling all the way to -150°C? Isn't that overkill? Actually, this extra cooling turns out to be crucial. Between the melting point (-38°C, where ice can start forming) and the glass transition temperature, we're in a dangerous middle ground. The molecules are moving slowly, sure, but "slowly" isn't good enough for long-term preservation. We need that extra margin of safety to ensure everything stays locked firmly in place.
After all this work preventing ice formation and stopping molecular motion, a big threat to preserved organs turns out to be the physical stresses that develop as different parts of the tissue cool at different rates.
Where biologists battled ice crystals and chemists refined cryoprotectants, Rabin contemplated the forces that engineers analyze in bridges and buildings.
What happens when different parts of an organ cool at different rates? Consider dropping an ice cube into warm water—that sharp crack you hear is thermal stress in action. Now imagine a heart, cooled until it's as brittle as glass, experiencing those same forces.
His insight was elegantly simple: materials behave differently at different temperatures. Heart tissue that flexes like rubber at room temperature becomes rigid and glass-like when cooled to low temperatures. And during preservation, an organ contains regions at various temperatures, creating an invisible network of pushing and pulling forces throughout.
By mapping these forces with engineering tools, Rabin revealed that even perfect vitrification wouldn't be enough. Mechanical stress during cooling and warming could still fracture organs from within. Perhaps the preservation challenge wasn't just chemical but mechanical. Maybe what we needed was better engineering.
If you were designing a container to preserve an organ in its glassy state, what shape would you choose? Your first instinct might be something simple and symmetrical, like a cylinder. Or maybe something that follows the organ's natural shape, like the flexible plastic bags currently used for tissue storage. It turns out this seemingly mundane choice matters far more than anyone expected.
Remember that engineering insight about different parts of the tissue cooling at different rates? Well, the container isn't just a passive box holding your organ - it actively shapes how heat flows through the tissue. Rabin's team compared two container designs: a standard plastic preservation bag and cylindrical containers of different sizes. When they mapped the mechanical stresses that developed during cooling and warming, they found something surprising: the same heart, preserved in the same way, experienced significantly different stress patterns depending on the container shape.
In some experiments, the cylindrical containers produced dramatically higher stress levels - up to 94% higher than the preservation bag in certain conditions. But perhaps more importantly, the location of that maximum stress changed completely. In the bag, the highest stresses occurred in various regions of the heart tissue itself. But in cylinders, the danger zone consistently shifted to the edge where the preservation solution contacted the container wall at the top of the cylinder.
You might think "well, just use a bigger container then - give everything more room." But Rabin's team found that scaling up the container size didn't help. When they doubled the cylinder's diameter, the peak stresses during rewarming actually increased by about 20% compared to the smaller cylinder.
What makes this so tricky is that the container affects preservation in multiple ways. Its shape influences how heat moves through the tissue. Its material properties determine how much the walls can flex as the contents cool and contract. Even the amount of preservation solution surrounding the organ matters - too little means uneven cooling, too much means longer warming times.
But perhaps the most counterintuitive finding was that the container's effects aren't consistent across scales. What works perfectly for preserving a rat heart might be disastrous for a human heart - not because bigger organs are inherently harder to preserve, but because the physics of heat flow and mechanical stress changes with size in surprising ways.
So far we've talked about getting tissue into its preserved, glass-like state. But eventually, you need to warm it back up again. And if you thought cooling was tricky, warming turns out to be even more challenging.
Why? Think about what's happening: you're taking tissue that's become literally as brittle as glass and trying to warm it evenly enough that it doesn't crack from thermal stress. Traditional warming methods heat from the outside in, like defrosting a frozen dinner. But preserved organs aren't frozen dinners - they're complex structures that need to warm uniformly to avoid developing the kinds of mechanical stresses that can shatter them.
Rabin’s team discovered that different parts of the heart create different mechanical challenges during warming. The heart chambers, for instance, tend to warm faster than the surrounding muscle tissue. This creates a complex pattern of forces: rapidly warming regions experience compression, while slower-warming regions experience tension. Remember - these tissues are still in their brittle, glass-like state, and like a glass window, they're much more likely to crack under tension than compression.
To solve this problem, scientists developed an ingenious approach: they add magnetic nanoparticles to the preservation solution. By exposing these particles to an alternating magnetic field, they can generate heat throughout the tissue rather than just at its surface. But Rabin's computational studies revealed a catch: the nanoparticles don't distribute evenly through the tissue. The heart chambers end up with higher concentrations than the heart muscle—with chambers containing nearly seven times more nanoparticles than the surrounding tissue—creating a variable distribution based on the heart's anatomy. This uneven heating creates complex thermal gradients that can actually amplify mechanical stress rather than reduce it. Rabin's models showed that optimizing nanoparticle concentration isn't just about getting enough particles, it's about achieving the right distribution pattern to counterbalance the natural stress profiles that develop during warming. Too few particles in the myocardium means insufficient warming, too many in the chambers means excessive thermal expansion—both scenarios leading to potential structural failure.
The nanoparticles Rabin's team uses aren't just any magnetic particles—they're specifically silica-coated iron oxide nanoparticles (sIONPs) that respond to radiofrequency fields in the 100-400 kHz range. This coating is crucial—it prevents the particles from clumping together while preserving their heating properties. When exposed to an alternating magnetic field, these particles generate heat through magnetic hysteresis, effectively turning each nanoparticle into a tiny heating element dispersed throughout the tissue. After warming is complete, these particles can be washed out of the organ with remarkable efficiency—experimental studies showed 93% removal in rat hearts, with the remaining particles well within tolerable concentrations.
It's not enough to just prevent ice formation or maintain low temperatures - we need to carefully choreograph the mechanical forces that develop during both cooling and warming. And as we'll see in our next article, when we try to scale these techniques up to human-sized organs, the challenge becomes even more interesting.
The challenge of scaling from rat to human hearts introduces an entirely new dimension of complexity. Rabin's computational models revealed that the patterns observed in rat hearts don't simply scale up linearly in human hearts. The larger geometry creates fundamentally different thermal gradients—heat takes longer to flow through the thicker human heart walls, creating steeper temperature differences during warming. These differences translate into completely different stress profiles. What works perfectly at the rat scale might fail when applied to human organs, not because the principles are wrong, but because the physics of heat transfer and mechanical stress changes with size in counter-intuitive ways. Successfully preserving human-sized organs will require rethinking thermal protocols—perhaps using staged warming with strategic pauses to allow the temperature to equalize throughout the tissue.
The journey from living tissue to preserved organ and back again isn't just about temperature control or chemical preservation. It's about understanding and controlling the mechanical forces that develop when materials as complex as living tissue undergo extreme transformations. As organs become glass-like at ultra-low temperatures, they become subject to the same kinds of mechanical stresses that engineers typically study in bridges or buildings. Every detail matters - from the shape of the container to the distribution of warming particles.
The stakes of this research extend far beyond the laboratory. Rabin and his colleagues note that 'if only one-half of the currently discarded hearts and lungs were utilized for transplantation, the waitlists for these organs could be eliminated within 2–3 years.' Each incremental improvement in preservation technology translates directly to lives saved—making the engineering challenges of cryopreservation not just scientific puzzles but humanitarian imperatives.