Shiraiwa, H. | bioRxiv Science

bioRxiv2026

Chlamylipo, a Chlamydomonas-in-liposome microswimmer: self-propelled swimming and associated lipid membrane flow

Developing active transport systems for microcargo delivery is challenging and requires overcoming the low Reynolds number constraints. We developed a bio-hybrid micro-swimmer, "chlamylipo" consisting of the green alga Chlamydomonas reinhardtii, encapsulated within a giant liposome. Although internal encapsulation offers cargo protection, it requires a mechanism to transmit the propulsion force across a closed membrane. We demonstrated that chlamylipo exhibited forward swimming and phototactic directional control. High-speed imaging of membrane shape and fluid flow revealed that the driving force originated from periodic membrane deformations and was accompanied by characteristic fluid dynamics. Flow analysis showed rapid oscillations at tens of hertz corresponding to flagellar beating, superimposed on slower axial migration at approximately 4 Hz associated with cell rotation. Corresponding flow signatures were also detected in the external fluid, indicating mechanical coupling across the lipid bilayer. Membrane domain tracking further showed that fluid motions inside and outside the membrane were coupled through viscous friction and membrane deformation, generating a characteristic four-vortex flow field consistent with a two-point force model. Together, these results suggest that membrane flow mainly reflects force transmission across the bilayer, whereas forward propulsion is primarily driven by periodic membrane deformation. This study elucidates the physical mechanism of force transmission in encapsulated swimmers, demonstrating that internal hydrodynamic power can effectively drive the motion of macroscopic containers. SignificanceThe development of autonomous micro-swimmers for targeted drug delivery is a major challenge in biophysics. We present "chlamylipo," a hybrid system in which a swimming alga is encapsulated inside a lipid vesicle. This study is significant because it demonstrates that an enclosed swimmer can propel a macroscopic container solely via hydrodynamic coupling across a closed membrane without direct external mechanical links. Furthermore, we achieved external directional control using phototaxis. This study provides physical insights into fluid-membrane interactions and proposes a novel strategy for designing light-guided active transport carriers.

biophysics↗

bioRxiv2022

Molecular engineering of emicizumab to improve hemophilia A treatment

Emicizumab, a factor (F)VIIIa-function mimetic bispecific antibody (BsAb) to FIXa and FX, has become an indispensable treatment for people with hemophilia A (PwHA). Although emicizumab is very potent, long-term outcomes from the clinical studies suggest that a small proportion of PwHA still experiences bleeds. Additionally, non-clinical studies indicate that the maximum cofactor activity of emicizumab is lower than international standard activity (100 IU/dL of FVIII). An increased cofactor activity BsAb would benefit such patients. Here, we report NXT007, a BsAb binding FIXa and FX developed through further engineering of emicizumab. Emicizumab has a common light chain, but through advances in antibody engineering, we were able to create a more potent BsAb with two new non-common light chains. After extensive optimization of the heavy and light chains, the resulting BsAb, NXT007, exerted in vitro thrombin generation (TG) activity in hemophilia A plasma equivalent to 100 IU/dL of FVIII when triggered by tissue factor. NXT007 demonstrated potent hemostatic activity in an acquired hemophilia A model in non-human primates at a much lower dosage than emicizumab, consistent with an around 30-fold dose shift in the in vitro TG activity between NXT007 and emicizumab. Moreover, together with Fc engineering that enhanced FcRn binding and reduced in vivo clearance, we demonstrate that NXT007 could be effective at a much lower dosage with a longer dosing interval compared to emicizumab. These non-clinical results suggest that NXT007 could maintain a non-hemophilic range of coagulation potential in PwHA and provides a rationale for its clinical testing.

bioengineering↗