Biohybrid microswimmer
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A biohybrid microswimmer also known as biohybrid nanorobot,[1] can be defined as a microswimmer that consist of both biological and artificial constituents, for instance, one or several living microorganisms attached to one or various synthetic parts.
In recent years
In addition, collective motion requires a coupling mechanism between the entities that make up the collective. To develop mesoscopic to nanoscopic entities capable of swarming behaviour, it has been hypothesised that the entities are characterised by broken symmetry with a well-defined morphology, and are powered with some material capable of harvesting energy. If the harvested energy results in a field surrounding the object, then this field can couple with the field of a neighbouring object and bring some coordination to the collective behaviour. Such
Over the past decade, biohybrid microrobots, in which living mobile microorganisms are physically integrated with untethered artificial structures, have gained growing interest to enable the active locomotion and cargo delivery to a target destination. In addition to the motility, the intrinsic capabilities of sensing and eliciting an appropriate response to artificial and environmental changes make cell-based biohybrid microrobots appealing for transportation of cargo to the inaccessible cavities of the human body for local active delivery of diagnostic and therapeutic agents.
Background
Biohybrid microswimmers can be defined as microswimmers that consist of both biological and artificial constituents, for instance, one or several living microorganisms attached to one or various synthetic parts.
One of the most fundamental questions in science is what defines life.[5] Collective motion is one of the hallmarks of life.[6] This is commonly observed in nature at various dimensional levels as energized entities gather, in a concerted effort, into motile aggregated patterns. These motile aggregated events can be noticed, among many others, as dynamic swarms; e.g., unicellular organisms such as bacteria, locust swarms, or the flocking behaviour of birds.[7][8][9]
Ever since Newton established his equations of motion, the mystery of motion on the microscale has emerged frequently in scientific history, as famously demonstrated by a couple of articles that should be discussed briefly. First, an essential concept, popularized by
Here, ρ represents the density of the fluid; u is a characteristic velocity of the system (for instance, the velocity of a swimming particle); l is a characteristic length scale (e.g., the swimmer size); and μ is the viscosity of the fluid. Taking the suspending fluid to be water, and using experimentally observed values for u, one can determine that inertia is important for macroscopic swimmers like fish (Re = 100), while viscosity dominates the motion of microscale swimmers like bacteria (Re = 10−4).[3]
The overwhelming importance of viscosity for swimming at the micrometer scale has profound implications for swimming strategy. This has been discussed memorably by
Microorganisms have optimized their
where is the velocity of the fluid and is the gradient of the pressure. As Purcell noted, the resulting equation — the Stokes equation — contains no explicit time dependence.[10] This has some important consequences for how a suspended body (e.g., a bacterium) can swim through periodic mechanical motions or deformations (e.g., of a flagellum). First, the rate of motion is practically irrelevant for the motion of the microswimmer and of the surrounding fluid: changing the rate of motion will change the scale of the velocities of the fluid and of the microswimmer, but it will not change the pattern of fluid flow. Secondly, reversing the direction of mechanical motion will simply reverse all velocities in the system. These properties of the Stokes equation severely restrict the range of feasible swimming strategies.[10][3]
Recent publications of biohybrid microswimmers include the use of sperm cells, contractive muscle cells, and bacteria as biological components, as they can efficiently convert chemical energy into movement, and additionally are capable of performing complicated motion depending on environmental conditions. In this sense, biohybrid microswimmer systems can be described as the combination of different functional components: cargo and carrier. The cargo is an element of interest to be moved (and possibly released) in a customized way. The carrier is the component responsible for the movement of the biohybrid, transporting the desired cargo, which is linked to its surface. The great majority of these systems rely on biological motile propulsion for the transportation of synthetic cargo for targeted drug delivery/[2] There are also examples of the opposite case: artificial microswimmers with biological cargo systems.[11][12][3]
Over the past decade, biohybrid microrobots, in which living mobile microorganisms are physically integrated with untethered artificial structures, have gained growing interest to enable the active locomotion and cargo delivery to a target destination.[13][14][15][16] In addition to the motility, the intrinsic capabilities of sensing and eliciting an appropriate response to artificial and environmental changes make cell-based biohybrid microrobots appealing for transportation of cargo to the inaccessible cavities of the human body for local active delivery of diagnostic and therapeutic agents.[17][18][19] Active locomotion, targeting and steering of concentrated therapeutic and diagnostic agents embedded in mobile microrobots to the site of action can overcome the existing challenges of conventional therapies.[20][21][22] To this end, bacteria have been commonly used with attached beads and ghost cell bodies.[23][24][25][26][27][28][29][30][31]
Bacterial biohybrids
Artificial micro and nanoswimmers are small scale devices that convert energy into movement.[33][12] Since the first demonstration of their performance in 2002, the field has developed rapidly in terms of new preparation methodologies, propulsion strategies, motion control, and envisioned functionality.[34][35] The field holds promise for applications such as drug delivery, environmental remediation and sensing. The initial focus of the field was largely on artificial systems, but an increasing number of "biohybrids" are appearing in the literature. Combining artificial and biological components is a promising strategy to obtain new, well-controlled microswimmer functionalities, since essential functions of living organisms are intrinsically related to the capability to move.[36] Living beings of all scales move in response to environmental stimuli (e.g., temperature or pH), to look for food sources, to reproduce, or to escape from predators. One of the more well-known living microsystems are swimming bacteria, but directed motion occurs even at the molecular scale, where enzymes and proteins undergo conformational changes in order to carry out biological tasks.[37][3]
Swimming bacterial cells have been used in the development of hybrid microswimmers.[38][39][40][41] Cargo attachment to the bacterial cells might influence their swimming behavior.[3] Bacterial cells in the swarming state have also been used in the development of hybrid microswimmers. Swarming Serratia marcescens cells were transferred to PDMS-coated coverslips, resulting in a structure referred to as a "bacterial carpet" by the authors. Differently shaped flat fragments of this bacterial carpets, termed "auto-mobile chips", moved above the surface of the microscope slide in two dimensions.[42] Many other works have used Serratia marcescens swarming cells,[43][44][45][46][47][48] as well as E. coli swarming cells [49][23] for the development of hybrid microswimmers.[3] Magnetotactic bacteria have been the focus of different studies due to their versatile uses in biohybrid motion systems.[50][51][52][53][54][3]
Protist biohybrids
Algal
Robocoliths
In recent years
Small mesoscopic to nanoscopic systems typically operate at low Reynolds numbers (Re ≪ 1), and understanding their motion becomes challenging.[69] For locomotion to occur, the symmetry of the system must be broken.14 In addition, collective motion requires a coupling mechanism between the entities that make up the collective.[61]
To develop mesoscopic to nanoscopic entities capable of swarming behaviour, it has been hypothesised that the entities are characterised by broken symmetry with a well-defined morphology, and are powered with some material capable of harvesting energy. If the harvested energy results in a field surrounding the object, then this field can couple with the field of a neighbouring object and bring some coordination to the collective behaviour.[61]
After the process is finished, the formed coccoliths are secreted to the cell surface, where they form the exoskeleton (i.e.,
Presumably, if harvesting of energy is done on both sides of the EHUX coccolith, then it will allow generation of a net force, which means movement in a directional manner. Coccoliths have immense potential for a multitude of applications, but to enable harvesting of energy, their surface properties must be finely tuned.[77] Inspired by the composition of adhesive proteins in mussels, dopamine self-polymerization into polydopamine is currently the most versatile functionalization strategy for virtually all types of materials.[78] Because of its surface chemistry and wide range of light absorption properties, polydopamine is an ideal choice for aided energy harvesting function on inert substrates.[79][80][81] In this work, we aim to exploit the benefits of polydopamine coating to provide advanced energy harvesting functionalities to the otherwise inert and inanimate coccoliths. Polydopamine (PDA has already been shown to induce movement of polystyrene beads because of thermal diffusion effects between the object and the surrounding aqueous solution of up to 2 °C under near-infrared (NIR) light excitation.[82] However, no collective behavior has been reported. Here, we prove, for the first time, that polydopamine can act as an active component to induce, under visible light (300–600 nm), collective behavior of a structurally complex, natural, and challenging-to-control architecture such as coccoliths. As a result, the organic-inorganic hybrid combination (coccolith-polydopamine) would enable design of Robocoliths.[61]
Dopamine polymerization proceeds in a solution, where it forms small colloidal aggregates that adsorb on the surface of the coccoliths, forming a confluent film. This film is characterized by high roughness, which translates into a high specific surface area and enhanced harvesting of energy. Because of the conjugated nature of the polymer backbone, polydopamine can absorb light over a broad electromagnetic spectrum, including the visible region.[61]
As a result, the surface of coccoliths is endowed with a photothermal effect, locally heating and creating convection induced by the presence of PDA. This local convection is coupled with another nearby local convection, which allows coupling between individual Robocoliths, enabling their collective motion (Figure 1).[61]
Therefore, when the light encounters the anisometric Robocoliths, they heat locally because of the photothermal conversion induced by the presence of PDA on their surface. The intense local heating produces convection that is different on either side of the Robocolith, causing its observed movement. Such convection can couple with the convection of a neighboring Robocolith, resulting in a "swarming" motion. In addition, the surface of Robocoliths is engineered to accommodate antifouling polymer brushes and potentially prevent their aggregation. Although a primary light-activated convective approach is taken as a first step to understand the motion of Robocoliths, a multitude of mechanistic approaches are currently being developed to pave the way for the next generation of multifunctional Robocoliths as swarming bio-micromachines.[61]
Biomedical applications
Biohybrid microswimmers, mainly composed of integrated biological actuators and synthetic cargo carriers, have recently shown promise toward minimally invasive
Bacteria have a high swimming speed and efficiency in the low Reynolds (Re) number flow regime, are capable of sensing and responding to external environmental signals, and could be externally detected via fluorescence or ultrasound imaging techniques.
On the other hand, specialised
Superior cargo-carrying properties of the RBCs have also generated increased interest for their use in biohybrid microswimmer designs. Recently, active navigation and control of drug and
References
- ^ https://jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01463-z
- ^ .
- ^ PMID 33500976. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
- S2CID 250910730.
- S2CID 119444389.
- ^ S2CID 119109873.
- PMID 20483315.
- PMID 22916003.
- PMID 31162047.
- ^ doi:10.1119/1.10903.
- ^ PMID 25415461.
- ^ PMID 26234432.
- S2CID 29776467.
- S2CID 139819519.
- PMID 29577477.
- PMID 24895215.
- .
- ^ PMID 27525475.
- ^ S2CID 52823884.
- PMID 28480466.
- PMID 31552379.
- ^ S2CID 88204894.
- ^ PMID 28873304.
- .
- .
- PMID 28638787.
- PMID 29955099.
- ^ PMID 28858477.
- PMID 28299891.
- PMID 28933815.
- ^ PMID 32832367. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
- PMID 28932674. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
- S2CID 55293424.
- .
- PMID 27809479.
- PMID 10753125.
- PMID 15939237.
- PMID 20457936.
- S2CID 40359976.
- S2CID 138755512.
- PMID 26940033.
- PMID 14990512.
- S2CID 6409992.
- .
- S2CID 36806.
- PMID 20422075.
- PMID 22304117.
- S2CID 15062290.
- .
- ^ Lu, Z., and Martel, S. (2006). "Preliminary investigation of bio-carriers using magnetotactic bacteria". In: Engineering in Medicine and Biology Society, 2006. EMBS'06. 28th Annual International Conference of the IEEE (New York, NY: IEEE), 3415–3418.
- PMID 18855486.
- S2CID 2894776.
- PMID 24684397.
- .
- ^ PMID 11337403.
- ^ PMID 16103369.
- PMID 24406198.
- S2CID 52922420.
- PMID 25536030.
- S2CID 46953567.
- ^ S2CID 233687429. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
- S2CID 89610765.
- PMID 26172380.
- .
- PMID 30393364.
- PMID 27658450.
- S2CID 3800579.
- PMID 26057233.
- ^ Nelson P.C. (2003) "Life in the slow lane: The low Reynolds-number world", In: Biological Physics: Energy, Information, Life, by W.H. Freeman, pages 158–194.
- ^ Karunadasa K.S.P., C.H. Manoratne, H.M.T.G.A. Pitawala and R.M.G. Rajapakse (2019) "Thermal decomposition of calcium carbonate (calcite polymorph) as examined by in-situ high-temperature X-ray powder diffraction", J. Phys. Chem. Solids, 134: 21–28.
- PMID 23938635.
- PMID 26762469.
- PMID 19006397.
- PMID 28822276.
- S2CID 139596031.
- PMID 28701909.
- S2CID 206176301.
- PMID 17947576.
- PMID 29465221.
- PMID 29510631.
- PMID 24517847.
- S2CID 203638540.
- ^ PMID 32548539. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
- PMID 32466116. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
- ISSN 2076-3417. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
- PMID 27641944.
- .
- PMID 33500976.
- PMID 16103369.
- PMID 29202221.
- S2CID 103392074.
- ^ S2CID 139819519.
- ^ S2CID 14003685.
- PMID 27555465.
- PMID 26073316.
- PMID 20944664.
- PMID 28501457.
- PMID 29300010.
- ^ Cann, S.H., Van Netten, J.P. and Van Netten, C. (2003) "Dr William Coley and tumour regression: a place in history or in the future", Postgraduate Medical Journal, 79(938): 672-680.
- PMID 28771926.
- PMID 820877.
- PMID 20299242.
- PMID 27051423.
- PMID 28637010.
- S2CID 3989795.
- PMID 17997501.
- PMID 27090487.
- PMID 26941164.
- .
- S2CID 205229117.
- PMID 19027156.
- PMID 23462967.
- PMID 23584215.
- S2CID 22401350.
- ^ PMID 24449438.
- PMID 28396605.
- PMID 29992966.