The novel Plasmodium berghei protein S14 is essential for sporozoite gliding motility and infectivity.

Plasmodium sporozoites are the infective forms of the malaria parasite in the mosquito and vertebrate host. Gliding motility allows sporozoites to migrate and invade mosquito salivary glands and mammalian hosts. Motility and invasion are powered by an actin-myosin motor complex linked to the glideosome, which contains glideosome-associated proteins (GAPs), MyoA and the myosin A tail-interacting protein (MTIP). However, the role of several proteins involved in gliding motility remains unknown. We identified that the S14 gene is upregulated in sporozoite from transcriptome data of Plasmodium yoelii and further confirmed its transcription in P. berghei sporozoites using real-time PCR. C-terminal 3×HA-mCherry tagging revealed that S14 is expressed and localized on the inner membrane complex of the sporozoites. We disrupted S14 in P. berghei and demonstrated that it is essential for sporozoite gliding motility, and salivary gland and hepatocyte invasion. The gliding and invasion-deficient S14 knockout sporozoites showed normal expression and organization of inner membrane complex and surface proteins. Taken together, our data show that S14 plays a role in the function of the glideosome and is essential for malaria transmission.

Conformational change of Plasmodium TRAP is essential for sporozoite migration and transmission.

Eukaryotic cell adhesion and migration rely on surface adhesins connecting extracellular ligands to the intracellular actin cytoskeleton. Plasmodium sporozoites are transmitted by mosquitoes and rely on adhesion and gliding motility to colonize the salivary glands and to reach the liver after transmission. During gliding, the essential sporozoite adhesin TRAP engages actin filaments in the cytoplasm of the parasite, while binding ligands on the substrate through its inserted (I) domain. Crystal structures of TRAP from different Plasmodium species reveal the I domain in closed and open conformations. Here, we probe the importance of these two conformational states by generating parasites expressing versions of TRAP with the I domain stabilized in either the open or closed state with disulfide bonds. Strikingly, both mutations impact sporozoite gliding, mosquito salivary gland entry, and transmission. Absence of gliding in sporozoites expressing the open TRAP I domain can be partially rescued by adding a reducing agent. This suggests that dynamic conformational change is required for ligand binding, gliding motility, and organ invasion and hence sporozoite transmission from mosquito to mammal.

Gliding motility proteins GldJ and SprB contribute to Flavobacterium columnare virulence.

Flavobacterium columnare causes columnaris disease in fish. Columnaris disease is incompletely understood, and adequate control measures are lacking. The type IX secretion system (T9SS) is required for F. columnare gliding motility and virulence. The T9SS and gliding motility machineries share some, but not all, components. GldN (required for gliding and for secretion) and PorV (involved in secretion but not required for gliding) are both needed for virulence, implicating T9SS-mediated secretion in virulence. The role of motility in virulence is uncertain. We constructed and analyzed sprB, sprF, and gldJ mutants that were defective for motility but that maintained T9SS function to understand the role of motility in virulence. Wild-type cells moved rapidly and formed spreading colonies. In contrast, sprB and sprF deletion mutants were partially defective in gliding and formed nonspreading colonies. Both mutants exhibited reduced virulence in rainbow trout fry. A gldJ deletion mutant was nonmotile, secretion deficient, and avirulent in rainbow trout fry. To separate the roles of GldJ in secretion and in motility, we generated gldJ truncation mutants that produce nearly full-length GldJ. Mutant gldJ563, which produces GldJ truncated at amino acid 563, was defective for gliding but was competent for secretion as measured by extracellular proteolytic activity. This mutant displayed reduced virulence in rainbow trout fry, suggesting that motility contributes to virulence. Fish that survived exposure to the sprB deletion mutant or the gldJ563 mutant exhibited partial resistance to later challenge with wild-type cells. The results aid our understanding of columnaris disease and may suggest control strategies.IMPORTANCEFlavobacterium columnare causes columnaris disease in many species of freshwater fish in the wild and in aquaculture systems. Fish mortalities resulting from columnaris disease are a major problem for aquaculture. F. columnare virulence is incompletely understood, and control measures are inadequate. Gliding motility and protein secretion have been suggested to contribute to columnaris disease, but evidence directly linking motility to disease was lacking. We isolated and analyzed mutants that were competent for secretion but defective for motility. Some of these mutants exhibited decreased virulence. Fish that had been exposed to these mutants were partially protected from later exposure to the wild type. The results contribute to our understanding of columnaris disease and may aid development of control strategies.

A brain specific alternatively spliced isoform of nonmuscle myosin IIA lacks its mechanoenzymatic activities.

Recent genomic studies reported that 90 to 95% of human genes can undergo alternative splicing, by which multiple isoforms of proteins are synthesized. However, the functional consequences of most of the isoforms are largely unknown. Here, we report a novel alternatively spliced isoform of nonmuscle myosin IIA (NM IIA), called NM IIA2, which is generated by the inclusion of 21 amino acids near the actin-binding region (loop 2) of the head domain of heavy chains. Expression of NM IIA2 is found exclusively in the brain tissue, where it reaches a maximum level at 24 h during the circadian rhythm. The actin-dependent Mg2+-ATPase activity and in vitro motility assays reveal that NM IIA2 lacks its motor activities but localizes with actin filaments in cells. Interestingly, NM IIA2 can also make heterofilaments with NM IIA0 (noninserted isoform of NM IIA) and can retard the in vitro motility of NM IIA, when the two are mixed. Altogether, our findings provide the functional importance of a previously unknown alternatively spliced isoform, NM IIA2, and its potential physiological role in regulating NM IIA activity in the brain.

Ensembles of human myosin-19 bound to calmodulin and regulatory light chain RLC12B drive multimicron transport.

Myosin-19 (Myo19) controls the size, morphology, and distribution of mitochondria, but the underlying role of Myo19 motor activity is unknown. Complicating mechanistic in vitro studies, the identity of the light chains (LCs) of Myo19 remains unsettled. Here, we show by coimmunoprecipitation, reconstitution, and proteomics that the three IQ motifs of human Myo19 expressed in Expi293 human cells bind regulatory light chain (RLC12B) and calmodulin (CaM). We demonstrate that overexpression of Myo19 in HeLa cells enhances the recruitment of both Myo19 and RLC12B to mitochondria, suggesting cellular association of RLC12B with the motor. Further experiments revealed that RLC12B binds IQ2 and is flanked by two CaM molecules. In vitro, we observed that the maximal speed (∼350 nm/s) occurs when Myo19 is supplemented with CaM, but not RLC12B, suggesting maximal motility requires binding of CaM to IQ-1 and IQ-3. The addition of calcium slowed actin gliding (∼200 nm/s) without an apparent effect on CaM affinity. Furthermore, we show that small ensembles of Myo19 motors attached to quantum dots can undergo processive runs over several microns, and that calcium reduces the attachment frequency and run length of Myo19. Together, our data are consistent with a model where a few single-headed Myo19 molecules attached to a mitochondrion can sustain prolonged motile associations with actin in a CaM- and calcium-dependent manner. Based on these properties, we propose that Myo19 can function in mitochondria transport along actin filaments, tension generation on multiple randomly oriented filaments, and/or pushing against branched actin networks assembled near the membrane surface.

In Situ Constructing Ultrastable Mechanical Integrity of Single-Crystalline LiNi0.9 Co0.05 Mn0.05 O2 Cathode by Interior and Exterior Decoration Strategy.

Planar gliding along with anisotropic lattice strain of single-crystalline nickel-rich cathodes (SCNRC) at highly delithiated states will induce severe delamination cracking that seriously deteriorates LIBs' cyclability. To address these issues, a novel lattice-matched MgTiO3 (MTO) layer, which exhibits same lattice structure as Ni-rich cathodes, is rationally constructed on single-crystalline LiNi0.9 Co0.05 Mn0.05 O2 (SC90) for ultrastable mechanical integrity. Intensive in/ex situ characterizations combined with theoretical calculations and finite element analysis suggest that the uniform MTO coating layer prevents direct contact between SC90 and organic electrolytes and enables rapid Li-ion diffusion with depressed Li-deficiency, thereby stabilizing the interfacial structure and accommodating the mechanical stress of SC90. More importantly, a superstructure is simultaneously formed in SC90, which can effectively alleviate the anisotropic lattice changes and decrease cation mobility during successive high-voltage de/intercalation processes. Therefore, the as-acquired MTO-modified SC90 cathode displays desirable capacity retention and high-voltage stability. When paired with commercial graphite anodes, the pouch-type cells with the MTO-modified SC90 can deliver a high capacity of 175.2 mAh g-1 with 89.8% capacity retention after 500 cycles. This lattice-matching coating strategy demonstrate a highly effective pathway to maintain the structural and interfacial stability in electrode materials, which can be a pioneering breakthrough in commercialization of Ni-rich cathodes.

Cranes soar on thermal updrafts behind cold fronts as they migrate across the sea.

Thermal soaring conditions above the sea have long been assumed absent or too weak for terrestrial migrating birds, forcing obligate soarers to take long detours and avoid sea-crossing, and facultative soarers to cross exclusively by costly flapping flight. Thus, while atmospheric convection does develop at sea and is used by some seabirds, it has been largely ignored in avian migration research. Here, we provide direct evidence for routine thermal soaring over open sea in the common crane, the heaviest facultative soarer known among terrestrial migrating birds. Using high-resolution biologging from 44 cranes tracked across their transcontinental migration over 4 years, we show that soaring performance was no different over sea than over land in mid-latitudes. Sea-soaring occurred predominantly in autumn when large water-air temperature difference followed mid-latitude cyclones. Our findings challenge a fundamental migration research paradigm and suggest that obligate soarers avoid sea-crossing not due to the absence or weakness of thermals but due to their low frequency, for which they cannot compensate with prolonged flapping. Conversely, facultative soarers other than cranes should also be able to use thermals over the sea. Marine cold air outbreaks, imperative to global energy budget and climate, may also be important for bird migration.

Turkey vultures tune their airspeed to changing air density.

Animals must tune their physical performance to changing environmental conditions, and the breadth of environmental tolerance may contribute to delineating the geographic range of a species. A common environmental challenge that flying animals face is the reduction of air density at high elevation and the reduction in the effectiveness of lift production that accompanies it. As a species, turkey vultures (Cathartes aura) inhabit a >3000 m elevation range, and fly considerably higher, necessitating that they accommodate for a 27% change in air density (0.890 to 1.227 kg m-3) through behavior, physiology or biomechanics. We predicted that birds flying at high elevation would maintain aerodynamic lift performance behaviorally via higher flight speeds, rather than increases in power output or local phenotypic adaptation. We used three-dimensional videography to track turkey vultures flying at three elevations, and data supported the hypothesized negative relationship between median airspeed and air density. Additionally, neither the ratio of horizontal speed to sinking speed nor flapping behavior varied with air density.

Plasmodium sporozoite disintegration during skin passage limits malaria parasite transmission.

During transmission of malaria-causing parasites from mosquitoes to mammals, Plasmodium sporozoites migrate rapidly in the skin to search for a blood vessel. The high migratory speed and narrow passages taken by the parasites suggest considerable strain on the sporozoites to maintain their shape. Here, we show that the membrane-associated protein, concavin, is important for the maintenance of the Plasmodium sporozoite shape inside salivary glands of mosquitoes and during migration in the skin. Concavin-GFP localizes at the cytoplasmic periphery and concavin(-) sporozoites progressively round up upon entry of salivary glands. Rounded concavin(-) sporozoites fail to pass through the narrow salivary ducts and are rarely ejected by mosquitoes, while normally shaped concavin(-) sporozoites are transmitted. Strikingly, motile concavin(-) sporozoites disintegrate while migrating through the skin leading to parasite arrest or death and decreased transmission efficiency. Collectively, we suggest that concavin contributes to cell shape maintenance by riveting the plasma membrane to the subtending inner membrane complex. Interfering with cell shape maintenance pathways might hence provide a new strategy to prevent a malaria infection.

Gliding motility of Plasmodium merozoites.

Plasmodium malaria parasites are obligate intracellular protozoans that use a unique form of locomotion, termed gliding motility, to move through host tissues and invade cells. The process is substrate dependent and powered by an actomyosin motor that drives the posterior translocation of extracellular adhesins which, in turn, propel the parasite forward. Gliding motility is essential for tissue translocation in the sporozoite and ookinete stages; however, the short-lived erythrocyte-invading merozoite stage has never been observed to undergo gliding movement. Here we show Plasmodium merozoites possess the ability to undergo gliding motility in vitro and that this mechanism is likely an important precursor step for successful parasite invasion. We demonstrate that two human infective species, Plasmodium falciparum and Plasmodium knowlesi, have distinct merozoite motility profiles which may reflect distinct invasion strategies. Additionally, we develop and validate a higher throughput assay to evaluate the effects of genetic and pharmacological perturbations on both the molecular motor and the complex signaling cascade that regulates motility in merozoites. The discovery of merozoite motility provides a model to study the glideosome and adds a dimension for work aiming to develop treatments targeting the blood stage invasion pathways.

The cyanobacterial taxis protein HmpF regulates type IV pilus activity in response to light.

Motility is ubiquitous in prokaryotic organisms including the photosynthetic cyanobacteria where surface motility powered by type 4 pili (T4P) is common and facilitates phototaxis to seek out favorable light environments. In cyanobacteria, chemotaxis-like systems are known to regulate motility and phototaxis. The characterized phototaxis systems rely on methyl-accepting chemotaxis proteins containing bilin-binding GAF domains capable of directly sensing light, and the mechanism by which they regulate the T4P is largely undefined. In this study we demonstrate that cyanobacteria possess a second, GAF-independent, means of sensing light to regulate motility and provide insight into how a chemotaxis-like system regulates the T4P motors. A combination of genetic, cytological, and protein-protein interaction analyses, along with experiments using the proton ionophore carbonyl cyanide m-chlorophenyl hydrazine, indicate that the Hmp chemotaxis-like system of the model filamentous cyanobacterium Nostoc punctiforme is capable of sensing light indirectly, possibly via alterations in proton motive force, and modulates direct interaction between the cyanobacterial taxis protein HmpF, and Hfq, PilT1, and PilT2 to regulate the T4P motors. Given that the Hmp system is widely conserved in cyanobacteria, and the finding from this study that orthologs of HmpF and T4P proteins from the distantly related model unicellular cyanobacterium Synechocystis sp. strain PCC6803 interact in a similar manner to their N. punctiforme counterparts, it is likely that this represents a ubiquitous means of regulating motility in response to light in cyanobacteria.

Pattern formation and polarity sorting of driven actin filaments on lipid membranes.

Collective motion of active matter is ubiquitously observed, ranging from propelled colloids to flocks of bird, and often features the formation of complex structures composed of agents moving coherently. However, it remains extremely challenging to predict emergent patterns from the binary interaction between agents, especially as only a limited number of interaction regimes have been experimentally observed so far. Here, we introduce an actin gliding assay coupled to a supported lipid bilayer, whose fluidity forces the interaction between self-propelled filaments to be dominated by steric repulsion. This results in filaments stopping upon binary collisions and eventually aligning nematically. Such a binary interaction rule results at high densities in the emergence of dynamic collectively moving structures including clusters, vortices, and streams of filaments. Despite the microscopic interaction having a nematic symmetry, the emergent structures are found to be polar, with filaments collectively moving in the same direction. This is due to polar biases introduced by the stopping upon collision, both on the individual filaments scale as well as on the scale of collective structures. In this context, positive half-charged topological defects turn out to be a most efficient trapping and polarity sorting conformation.

A conserved Plasmodium structural integrity maintenance protein (SIMP) is associated with sporozoite membrane and is essential for maintaining shape and infectivity.

Plasmodium sporozoites are extracellular forms introduced during mosquito bite that selectively invade mammalian hepatocytes. Sporozoites are delimited by a cell membrane that is linked to the underlying acto-myosin molecular motor. While membrane proteins with roles in motility and invasion have been well studied, very little is known about proteins that maintain the sporozoite shape. We demonstrate that in Plasmodium berghei (Pb) a conserved hypothetical gene, PBANKA_1422900 specifies sporozoite structural integrity maintenance protein (SIMP) required for maintaining the sporozoite shape and motility. Sporozoites lacking SIMP exhibited loss of regular shape, extensive membrane blebbing at multiple foci, and membrane detachment. The mutant sporozoites failed to infect hepatocytes, though the altered shape did not affect the organization of cytoskeleton or inner membrane complex (IMC). Interestingly, the components of IMC failed to extend under the membrane blebs likely suggesting that SIMP may assist in anchoring the membrane to IMC. Endogenous C-terminal HA tagging localized SIMP to membrane and revealed the C-terminus of the protein to be extracellular. Since SIMP is highly conserved among Plasmodium species, these findings have important implications for utilizing it as a novel sporozoite-specific vaccine candidate.

Their fates intertwined: diversification patterns of the Asian gliding vertebrates may have been forged by dipterocarp trees.

The repeated evolution of gliding in diverse Asian vertebrate lineages is hypothesized to have been triggered by the dominance of tall dipterocarp trees in the tropical forests of Southeast Asia. These dipterocarp forests have acted as both centres of diversification and climatic refugia for gliding vertebrates, and support most of their extant diversity. We predict similarities in the diversification patterns of dipterocarp trees and gliding vertebrates, and specifically test whether episodic diversification events such as rate shifts and/or mass extinctions were temporally congruent in these groups. We analysed diversification patterns in reconstructed timetrees of Asian dipterocarps, the most speciose gliding vertebrates from different classes (Draco lizards, gliding frogs and Pteromyini squirrels) and compared them with similar-sized clades of non-gliding relatives (Diploderma lizards, Philautus frogs and Callosciurinae squirrels) from Southeast Asia. We found significant declines in net-diversification rates of dipterocarps and the gliding vertebrates during the Pliocene-Pleistocene, but not in the non-gliding groups. We conclude that the homogeneity and temporal coincidence of these rate declines point to a viable ecological correlation between dipterocarps and the gliding vertebrates. Further, we suggest that while the diversification decay in dipterocarps was precipitated by post-Miocene aridification of Asia, the crises in the gliding vertebrates were induced by both events concomitantly.

Diatom adhesive trail proteins acquired by horizontal gene transfer from bacteria serve as primers for marine biofilm formation.

Biofilm-forming benthic diatoms are key primary producers in coastal habitats, where they frequently dominate sunlit intertidal substrata. The development of gliding motility in raphid diatoms was a key molecular adaptation that contributed to their evolutionary success. However, the structure-function correlation between diatom adhesives utilized for gliding and their relationship to the extracellular matrix that constitutes the diatom biofilm is unknown. Here, we have used proteomics, immunolocalization, comparative genomics, phylogenetics and structural homology analysis to investigate the evolutionary history and function of diatom adhesive proteins. Our study identified eight proteins from the adhesive trails of Craspedostauros australis, of which four form a new protein family called Trailins that contain an enigmatic Choice-of-Anchor A (CAA) domain, which was acquired through horizontal gene transfer from bacteria. Notably, the CAA-domain shares a striking structural similarity with one of the most widespread domains found in ice-binding proteins (IPR021884). Our work offers new insights into the molecular basis for diatom biofilm formation, shedding light on the function and evolution of diatom adhesive proteins. This discovery suggests that there is a transition in the composition of biomolecules required for initial surface colonization and those utilized for 3D biofilm matrix formation.

Rheotaxis in Mycoplasma gliding.

This review describes the upstream-directed movement in the small parasitic bacterium Mycoplasma. Many Mycoplasma species exhibit gliding motility, a form of biological motion over surfaces without the aid of general surface appendages such as flagella. The gliding motility is characterized by a constant unidirectional movement without changes in direction or backward motion. Unlike flagellated bacteria, Mycoplasma lacks the general chemotactic signaling system to control their moving direction. Therefore, the physiological role of directionless travel in Mycoplasma gliding remains unclear. Recently, high-precision measurements under an optical microscope have revealed that three species of Mycoplasma exhibited rheotaxis, that is, the direction of gliding motility is lead upstream by the water flow. This intriguing response appears to be optimized for the flow patterns encountered at host surfaces. This review provides a comprehensive overview of the morphology, behavior, and habitat of Mycoplasma gliding, and discusses the possibility that the rheotaxis is ubiquitous among them.

Structure and function of an atypical homodimeric actin capping protein from the malaria parasite.

Apicomplexan parasites, such as Plasmodium spp., rely on an unusual actomyosin motor, termed glideosome, for motility and host cell invasion. The actin filaments are maintained by a small set of essential regulators, which provide control over actin dynamics in the different stages of the parasite life cycle. Actin filament capping proteins (CPs) are indispensable heterodimeric regulators of actin dynamics. CPs have been extensively characterized in higher eukaryotes, but their role and functional mechanism in Apicomplexa remain enigmatic. Here, we present the first crystal structure of a homodimeric CP from the malaria parasite and compare the homo- and heterodimeric CP structures in detail. Despite retaining several characteristics of a canonical CP, the homodimeric Plasmodium berghei (Pb)CP exhibits crucial differences to the canonical heterodimers. Both homo- and heterodimeric PbCPs regulate actin dynamics in an atypical manner, facilitating rapid turnover of parasite actin, without affecting its critical concentration. Homo- and heterodimeric PbCPs show partially redundant activities, possibly to rescue actin filament capping in life cycle stages where the ß-subunit is downregulated. Our data suggest that the homodimeric PbCP also influences actin kinetics by recruiting lateral actin dimers. This unusual function could arise from the absence of a ß-subunit, as the asymmetric PbCP homodimer lacks structural elements essential for canonical barbed end interactions suggesting a novel CP binding mode. These findings will facilitate further studies aimed at elucidating the precise actin filament capping mechanism in Plasmodium.

Cytoskeletal diversification across 1 billion years: What red algae can teach us about the cytoskeleton, and vice versa.

The cytoskeleton has a central role in eukaryotic biology, enabling cells to organize internally, polarize, and translocate. Studying cytoskeletal machinery across the tree of life can identify common elements, illuminate fundamental mechanisms, and provide insight into processes specific to less-characterized organisms. Red algae represent an ancient lineage that is diverse, ecologically significant, and biomedically relevant. Recent genomic analysis shows that red algae have a surprising paucity of cytoskeletal elements, particularly molecular motors. Here, we review the genomic and cell biological evidence and propose testable models of how red algal cells might perform processes including cell motility, cytokinesis, intracellular transport, and secretion, given their reduced cytoskeletons. In addition to enhancing understanding of red algae and lineages that evolved from red algal endosymbioses (e.g., apicomplexan parasites), these ideas may also provide insight into cytoskeletal processes in animal cells.

Establishing rod shape from spherical, peptidoglycan-deficient bacterial spores.

Chemical-induced spores of the Gram-negative bacterium Myxococcus xanthus are peptidoglycan (PG)-deficient. It is unclear how these spherical spores germinate into rod-shaped, walled cells without preexisting PG templates. We found that germinating spores first synthesize PG randomly on spherical surfaces. MglB, a GTPase-activating protein, forms a cluster that responds to the status of PG growth and stabilizes at one future cell pole. Following MglB, the Ras family GTPase MglA localizes to the second pole. MglA directs molecular motors to transport the bacterial actin homolog MreB and the Rod PG synthesis complexes away from poles. The Rod system establishes rod shape de novo by elongating PG at nonpolar regions. Thus, similar to eukaryotic cells, the interactions between GTPase, cytoskeletons, and molecular motors initiate spontaneous polarization in bacteria.

The Effect of Flexor Carpi Ulnaris Pulley Design on Tendon Gliding Resistance After Flexor Digitorum Superficialis Tendon Transfer for Opposition Transfer.

PURPOSE: The flexor digitorum superficialis (FDS) tendon transfer can be used to restore opposition of the thumb. Several pulley designs have been proposed for this transfer. Gliding resistance is considered to be an important factor influencing the efficiency of the pulley design. Our purpose was to compare the gliding resistance among 4 commonly used pulleys for the FDS oppositional transfer. METHODS: Ten fresh-frozen cadaver specimens were studied. The ring FDS was used as the donor tendon. An oppositional transfer was created using 4 pulley configurations: FDS passed around the flexor carpi ulnaris (a-FCU), FDS passed through a 2.5-cm circumference distally based FCU loop (2.5-FCU), FDS passed through a 3.5-cm circumference distally based FCU loop (3.5-FCU), and FDS passed through a longitudinal split in the FCU tendon (s-FCU). The gliding resistance was measured with the thumb in radial abduction and maximum opposition. RESULTS: In abduction, the average FDS gliding resistance of a-FCU, 2.5-FCU, 3.5-FCU, and s-FCU was 0.66 N (SD, 0.14 N), 0.70 N (SD, 0.14 N), 0.68 N (SD, 0.16 N), and 0.79 N (SD, 0.15 N), respectively. The peak gliding resistance of a-FCU, 2.5-FCU, 3.5-FCU, and s-FCU was 0.75 N (SD, 0.16 N), 0.74 N (SD, 0.15 N), 0.74 N (SD, 0.15 N), and 0.86 N (SD, 0.15 N), respectively. CONCLUSIONS: The average gliding resistance of the s-FCU was found to be significantly higher than that of the a-FCU and 3.5-FCU pulleys. In opposition, there were no differences in average or peak gliding resistance among the different pulley designs. CLINICAL RELEVANCE: In this in vitro cadaveric study, the FDS split pulley produced higher gliding resistance. Consideration of the pulley configuration may improve the overall thumb function by decreasing forces needed to overcome gliding resistance.