PHOTO CREDIT: University of Utah
A simulation of an ice inhibiting molecule. The molecule, in red, is like a weight on the surface of the ice crystal, curving it and preventing further ice crystal growth.
Cell therapies hold great promise for revolutionizing the treatment of cancers and autoimmune diseases. But this multibillion-dollar industry requires long-term storage of cells at super-cold cryogenic conditions, while ensuring they’ll continue to function upon thawing. However, these cold temperatures trigger the formation and growth of ice, which can pierce and tear apart cells. Research published in the Journal of the American Chemical Society by University of Utah chemists Pavithra Naullage and Valeria Molinero provides the foundation to design efficient polymers that can prevent the growth of ice that damages cells.
Current strategies to cryopreserve cells and organs involve bathing them with large amounts of dimethyl sulfoxide, a toxic chemical that messes up ice formation but stresses the cells, decreasing their odds for survival.
Nature, however, has found a way to keep organisms alive under extreme cold conditions: antifreeze proteins. Fish, insects and other cold-blooded organisms have evolved potent antifreeze glycoproteins that bind to ice crystallites and halt them from growing and damaging cells.
The growing area of cell-based therapeutics demands the development of potent inhibitors of ice recrystallization that can compete in activity with natural antifreeze glycoproteins but do not have the cost and toxicity of dimethyl sulfoxide. This demand has propelled the synthesis of polymers that mimic the action of antifreeze glycoproteins. But the most potent synthetic ice recrystallization inhibitor found to date, polyvinyl alcohol (PVA), is orders of magnitude less potent than natural glycoproteins.
“Efforts to identify stronger inhibitors for ice growth seem to have stalled, as there is not yet a molecular understanding of the factors that limits the ice recrystallization inhibition efficiency of polymers,” Molinero says.
A hidden polymer design variable
How do molecules prevent ice crystals from getting bigger? Molecules that bind strongly to ice pin its surface—like stones on a pillow—making the ice front develop a curved surface around the molecules. This curvature destabilizes the ice crystal, halting its growth. Molecules that stay bound to ice for times longer than the time it takes to grow ice crystals succeed in preventing further growth and recrystallization.
Molinero and Naullage used large-scale molecular simulations to elucidate the molecular underpinnings of how flexibility, length and functionalization of polymers control their binding to ice and their efficiency to prevent ice growth. Their study shows that the bound time of the molecules at the ice surface is controlled by the strength of their ice binding coupled with the length of the polymer and how fast they propagate on the ice surface.
“We found that the efficiency of flexible polymers in halting ice growth is limited by the slow propagation of their binding to ice,” Molinero says.
The study dissects the various factors that control the binding of flexible polymers to ice and that account for the gap in potency of PVA and natural antifreeze glycoproteins. In a nutshell, each block of antifreeze glycoproteins binds more strongly to ice than PVA does, and are also favored by their secondary molecular structure that segregates the binding and non-binding blocks to allow them to attach faster to ice to stop its growth.
“To our knowledge, this work is first to identity the time of propagation of binding as a key variable in the design of efficient ice-binding flexible polymers,” Naullage says. “Our study sets the stage for the de novo design of flexible polymers that can meet or even surpass the efficiency of antifreeze glycoproteins and make an impact in biomedical research.”
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
- A California man was the first to be cryogenically frozen. His body is still awaiting revival.
For 55 years, he’s rested in a metal tube: the first man in human history to be cryogenically frozen. The story is fraught with strangeness, complications and, depending on how you view cryogenics, ...
- Process Operator in Cryogenics
Job description Come and join the team of operators of the LHC cryogenic facilities, a unique opportunity to work on machines that constitute nearly half the world's stock of large helium liquefiers.
- VOX POPULI: Ensuring Japan’s vaccine rollout succeeds hinges on cryogenics
VOX POPULI: Ensuring Japan’s vaccine rollout succeeds hinges on cryogenics Vox Populi, Vox Dei is a daily column that runs on Page 1 of The Asahi Shimbun. February 18, 2021 at 13:23 JST ...
- Ratermann Manufacturing appoints Director of Operations
Ratermann Manufacturing has appointed Sven Brandau as its new Director of Operations. Brandau joins the cryogenic and compressed gas specialist from NCR, where he spent eight years focusing on supply ...
'I Used Kevin Durant's Story As A Launching Pad': Reggie Rock Bythewood On AppleTV+'s 'Swagger'The director talks about creating a TV show inspired by NBA superstar Kevin Durant's youth basketball ...
Go deeper with Google Headlines on:
Go deeper with Bing News on:
- Antifreeze Proteins Market 2022-2029 | Opportunities, Challenges, Key Players, Trend and Forecast
Global Antifreeze Proteins Market research report guides organization to achieve vital information about the competitors, economic shifts, demographics, current market trends and spending traits ...
- Antifreeze Proteins Market 2021 with Top Key Vendors like Nichirei Corporation, Kaneka Corporation, A/F Protein Inc
(MENAFN- Introspective Market Research) Global Antifreeze Proteins Market was valued at USD 2.55 Million in 2021 and is projected to reach USD 23.10 Million by 2027, growing at a CAGR of 28.50% ...
- 4 Penny Stocks Insiders Are Buying
When insiders purchase or sell shares, it indicates their confidence or concern around the company's prospects. Investors and traders interested in penny stocks can consider this a factor in their ...
- Convergent Evolution:
As scientists discovered in the 1960s, the fish have adapted by evolving a kind of antifreeze. It's composed of molecules called glycoproteins that circulate in the blood of the fishes ...
- Physiological Optima and Critical Limits
Some organisms live in environments that are colder than their freezing point and survive through supercooling or the use of antifreeze molecules. Colligative properties: Those properties of ...