- American Physical Society Sites
- Meetings & Events
- Policy & Advocacy
- Careers In Physics
- About APS
- Become a Member
By Sophia Chen
The human body is full of tiny machines.
No, this isn’t a conspiracy theory: Your cells contain countless proteins that help you convert food, or chemical fuel, into motion. When your heart muscle contracts or your chromosomes pull apart during cell division, these molecular machines are hard at work. This year’s APS March Meeting featured three sessions on such machines, including those that occur naturally and those designed by humans.
“Molecular machines” convert chemical energy into mechanical work and range in size from nanometers to hundreds of nanometers. Most naturally occurring molecular machines consist of proteins. These include myosin, which binds to muscle filaments to cause contraction, and kinesin, which shuttles molecules around cells in a walk-like motion. Many of these machines are also extremely efficient. The enzyme ATP synthase, for example, converts nearly 100 percent of free energy into mechanical work to create ATP, a molecule that provides energy to cells.
Research of these machines has taken off since the 1990s, with the rise of single-molecule manipulation and imaging techniques, says Nancy Forde of Simon Fraser University in Canada. Their study could reveal how cells interact with each other, a vital step toward understanding biological processes.
Credit: Kateryna Kon, Adobe Stock
An illustration of E. coli bacteria, with tail-like flagella visible. At the 2022 APS March Meeting, Jasmine Nirody discussed her research on the E. coli “flagellar motor,” an example of a tiny “molecular machine.”
Some researchers, seeking to apply this research, have begun engineering tiny systems that use or are inspired by naturally occurring molecular machines. Recently, Ken’ya Furuta, of Japan’s National Institute of Information and Communications Technology, replaced the “feet” of the protein dynein so that it could carry its cargo along a strand of DNA, instead of along the microtubule structures that make up its normal route in cells. Similar artificial machines could eventually be used to deliver drugs to target systems or to control chemical reactions.
Shoichi Toyabe of Tohoku University in Japan presented recent work on ATP synthase, a protein found in the mitochondria of human cells and virtually all other organisms. ATP synthase has two “motors,” F0 and F1. F0 drives F1, and F1 catalyzes the synthesis of ATP, rotating 120 degrees to do so.
Toyabe’s team was interested in F1. Why and how did the F1 motor preferentially rotate in one direction? To find out, the team placed isolated proteins on a probe, which they rotated using a changing electric field. The team found that ATP synthase has a mechanism that prevents the F1 motor from reversing, which they call “rectification,” in analogy with an electric circuit, where a rectifier only allows current to flow in one direction. The work raises the question of whether other proteins also encourage cellular processes to proceed in a certain direction. Eventually, Toyabe hopes to build an artificial machine, inspired by the F1 motor, out of DNA.
Jasmine Nirody, a postdoc with joint appointments at Rockefeller University and Oxford University, presented research on flagella, the hairlike appendages that cells use to propel themselves (picture the single flagellum, or “tail,” of a sperm cell). A bacterium’s flagellum propels it via rotation, powered by ion gradients between the interior and exterior of the cell.
Research on the flagellum could inform the design of more adaptable artificial molecular machines, according to Nirody. While human-designed motors can usually only function in specific conditions, she says, “the flagellar motor navigates these heterogeneous and unpredictable environments within cells. That aspect is fascinating and something that we can really learn from.”
At the 2022 APS March Meeting, Nirody presented a new flagellum model, an update based on detailed cryo-EM images released by researchers in 2020. The new images revealed that the flagellum rotates like a gear, driven by another rotating component.
Nirody’s work, like Toyabe’s, could help researchers design better molecular machines. “What has evolution done that we haven't figured out how to do?” Nirody says.
Nancy Forde, presenting work led by her graduate student, Chapin Korosec, introduced an artificial molecular machine they had created, dubbed “the lawnmower,” the outcome of a 15-year international collaboration between biologists, condensed matter physicists, and nanoscientists. The lawnmower is an artificial, nanoscale spherical bead covered in trypsin, a protein in the digestive system that breaks down other proteins. When the lawnmower is placed on an engineered surface covered in molecules called peptides, it cleaves the peptides, cutting them like grass in a yard. The lawnmower also powers itself, harnessing free energy released from the clipped peptides to continue moving.
The lawnmower’s design draws inspiration from the influenza virus, which is also spherical, sticks to cells, and cleaves cell receptors.
While Forde’s team could not control the lawnmower’s trajectory, they found that the lawnmower moved in a biased direction away from regions it had already mowed. Its average speed reached 60 nanometers per second, which is about the rate that grass grows.
Forde aims to use the underlying architecture of the lawnmower to create other types of molecular machines. They designed the lawnmower to be modular, so researchers can easily change its design—swapping the trypsin for another protein, for example, or changing the size of the quantum dot to tailor it for a specific application.
Eventually, Forde hopes to create molecular machines that can do “what nature has evolved proteins to be able to do,” she says. “It gives you this amazing appreciation of what nature has managed to evolve.”
Sophia Chen is a writer based in Columbus, Ohio.
©1995 - 2024, AMERICAN PHYSICAL SOCIETY
APS encourages the redistribution of the materials included in this newspaper provided that attribution to the source is noted and the materials are not truncated or changed.
APS (American Physical Society) - Mkutano wa Maonyesho na Matukio - Sera na Utetezi - Kazi katika Fizikia - Kuhusu APS - Kuwa Mwanachama - Sophia Chen - Mwili wa binadamu ni kamili ya mashine ndogo. La, hii si nadharia ya njama: Chembe zako zina protini nyingi sana ambazo hukusaidia kubadilisha chakula, au mafuta ya kemikali, kuwa mwendo. Wakati misuli ya moyo unapopungua au chromosomes zinapogawanyika wakati wa kugawanyika kwa seli, mashine hizi za molekuli zinafanya kazi kwa bidii. Mkutano wa Machi wa APS wa mwaka huu ulionyesha vikao vitatu kwenye mashine kama hizo, pamoja na zile zinazotokea kwa asili na zile zilizobuniwa na wanadamu. "Mashine za molekuli" hubadilisha nishati ya kemikali kuwa kazi ya mitambo na zina ukubwa wa nanometers hadi mamia ya nanometers. Mashine nyingi za molekuli zinazopatikana kiasili hufanyizwa na protini. Miongoni mwao ni myosin, ambayo huunganishwa na nyuzi za misuli ili kusababisha kupungua, na kinesin, ambayo husafirisha molekuli kuzunguka chembe kwa mwendo unaofanana na kutembea. Mashine hizo nyingi pia zina ufanisi mkubwa sana. Enzyme ya ATP synthase, kwa mfano, hubadilisha karibu asilimia 100 ya nishati ya bure kuwa kazi ya mitambo ili kuunda ATP, molekuli inayotoa nishati kwa chembe. "Utafiti wa mashine hizi umeanza tangu miaka ya 1990, na kuongezeka kwa mbinu za udhibiti wa molekuli moja na mbinu za picha, ""anasema Nancy Ford wa Chuo Kikuu cha Simon Fraser nchini Canada." Utafiti wao ungeweza kufunua jinsi chembe zinavyoingiliana, hatua muhimu kuelekea kuelewa taratibu za kibiolojia. Kateryna Kon, Adobe Stock Mchoro wa bakteria ya E. coli, yenye alama inayoonekana kama mkia. Katika mkutano wa APS wa Machi 2022, Jasmine Nirody alizungumzia utafiti wake juu ya E. coli - injini ya flagellate, mfano wa mashine ndogo ya molekuli - watafiti wengine, wakitafuta kutumia utafiti huu, wameanza kubuni mifumo midogo ambayo hutumia au imeongozwa na mashine za molekuli zinazotokea kwa asili. Hivi karibuni, Kenji Furuta, wa Taasisi ya Kitaifa ya Teknolojia ya Habari na Mawasiliano ya Japani, alibadilisha "mguu" wa protini ya dynein ili iweze kubeba mzigo wake kando ya nyuzi za DNA, badala ya kando ya miundo ya microtubules ambayo huunda njia yake ya kawaida katika seli. Mashine kama hizo za bandia zaweza kutumiwa hatimaye kutoa dawa kwa mifumo inayolengwa au kudhibiti athari za kemikali. Shoichi Toyabe, Mtaalamu wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti wa Utafiti. ATP synthase ina mbili <unk>motors,<unk> F0 na F1. F1 na F2 huendesha ATP na F1 huendesha ATP kwa kugeuka kwa digrii 120. Timu ya Toyabe ilipendezwa na F1. Kwa nini injini ya F1 ilizunguka kwa njia moja? Ili kujua, kikundi hicho kiliweka protini zilizotengwa kwenye chombo cha kuchunguza, ambacho kilizungushwa kwa kutumia uwanja wa umeme uliobadilika-badilika. "Timu hiyo iligundua kwamba ATP synthase ina utaratibu ambao unazuia injini ya F1 kutoka kwa kugeuka, ambayo wanaita ""kurudisha,"" kwa kulinganisha na mzunguko wa umeme, ambapo rectifier inaruhusu tu mkondo wa mtiririko katika mwelekeo mmoja." Kazi hiyo inaibua swali la ikiwa protini nyingine pia huchochea michakato ya chembe kuendelea katika mwelekeo fulani. Toyabe anatarajia kutengeneza mashine ya kiutendaji ya kuendesha gari la F1 Jasmine Nirdie, PhD na uteuzi wa pamoja katika Chuo Kikuu cha Rockefeller na Chuo Kikuu cha Oxford, alitoa utafiti juu ya flagella, nyongeza za nywele ambazo seli hutumia kujiendesha (picha ya flagellum moja, au <unk> mkia, <unk> wa seli ya shahawa). Aum's flagellum propels it kupitia mzunguko, powered na gradients ion kati ya ndani na nje ya seli. Kulingana na Nirody, utafiti kuhusu flagellum unaweza kusaidia kutengeneza mashine za molekuli za bandia zinazoweza kubadilika-badilika. Wakati motors binadamu iliyoundwa kwa kawaida inaweza tu kazi katika hali maalum, yeye anasema, <unk>motor flagellar navigates hizi mazingira heterogeneous na unpredictable ndani ya seli. "Kama mfano, katika mkutano wa APS wa Machi 2020, Nirodya aliwasilisha mfano mpya wa flagellum, ""mabadiliko kulingana na picha za kina za cryo-EM zilizotolewa na watafiti mnamo 2020.""" Picha hizo mpya zilionyesha kwamba kiwambo hicho kinazunguka-zunguka kama gia, kikiongozwa na sehemu nyingine inayozunguka. Kazi ya Nirody, kama ile ya Toyabe, yaweza kuwasaidia watafiti kubuni mashine bora za molekuli. "Mageuzi yamefanya nini ambacho hatujajua jinsi ya kufanya?" anasema Nirody. "Nancy Ford, akitoa kazi iliyoongozwa na mwanafunzi wake wa kuhitimu, Chapin Korosek, alianzisha mashine ya molekuli ya bandia ambayo walikuwa wameunda, inayoitwa ""mashine ya kukata nyasi,"" matokeo ya ushirikiano wa kimataifa wa miaka 15 kati ya wanabiolojia, fizikia wa nyenzo iliyofupishwa, na wanasayansi wa nanoscience." Mshono wa nyasi ni kioo cha nanoscale kilichofunikwa na trypsin, protini katika mfumo wa kumeng'enya ambayo huvunja protini nyingine. Wakati mashine ya kukata nyasi imewekwa kwenye uso uliofunikwa kwa molekuli zinazoitwa peptidi, inagawanya peptidi, ikiwakata kama nyasi katika bustani. Mashine ya kukata nyasi pia hujitoa yenyewe nguvu, ikitumia nishati ya bure inayotolewa na peptidi zilizokatwa ili kuendelea kusonga. Muundo wa mashine ya kukata nyasi unachochewa na virusi vya mafua, ambavyo pia ni vya mviringo, vinaambatana na chembe, na kuvunja vipokezi vya chembe. Ingawa timu ya Forde haikuweza kudhibiti mwendo wa mashine ya kukata nyasi, waligundua kwamba mashine ya kukata nyasi ilihama katika mwelekeo wa upendeleo mbali na maeneo ambayo tayari ilikuwa imekata. Kiwango cha juu cha mwendo wa mimea hiyo ni nanometer 60 kwa sekunde, ambayo ni sawa na mwendo wa ukuaji wa nyasi. Forde anakusudia kutumia usanifu wa msingi wa mashine ya kukata nyasi ili kuunda aina nyingine za mashine za molekuli. Kwa mfano, watafiti wanaweza kubadilisha muundo wake kwa kubadilisha trypsin kwa protini nyingine, au kubadilisha ukubwa wa nukta ya quantum ili kuibadilisha kwa matumizi maalum. Hatimaye, Forde anatumaini kuunda mashine za molekuli ambazo zinaweza kufanya "kile ambacho asili imebadilisha protini kuwa na uwezo wa kufanya", anasema. "Sophia Chen ni mwandishi anayeishi Columbus, Ohio.""" APS inahimiza usambazaji wa vifaa vilivyojumuishwa katika gazeti hili ikiwa ni pamoja na sifa kwa chanzo na vifaa havibadilishwi au kubadilishwa.