The research team led by Professor Wei Qiang, Chief Scientist of Maybio, Publishes Latest Research Findings in Global Top Stem Cell Journal Cell Stem Cell

Professor Wei Qiang, Chief Scientist at Maybio, and his research team, in collaboration with Professor Cao Yi's team from Nanjing University, releases: "Photo-tunable hydrogels reveal cellular sensing of rapid rigidity changes through the accumulation of mechanical signaling molecules"

Recently, The research team led by Professor Wei Qiang, Chief Scientist of Maybio, in collaboration with Professor Cao Yi's team from Nanjing University, published an article titled "Photo-Tunable Hydrogels Reveal Cellular Sensing of Rapid Rigidity Changes through Accumulation of Mechanical Signaling Molecules" in Cell Stem Cell—a sub-journal of one of the world's three top-tier academic journals Cell, a heavyweight journal in the life sciences field and a globally top-tier journal in the stem cell field. This journal primarily publishes research achievements and practices in biology-cell biology-related fields, aiming to create an academic journal with high scholarly standards, strong readability, and global influence.

The research team utilized hydrogel with photo-responsive rigidity to reveal that cells' response to rigidity changes is frequency dependent. It emphasizes the significance of dynamic rigidity in the development of synthetic biomaterials, emphasizing the importance of considering both immediate and prolonged cellular responses.

Key Research Sections

(1) Light-Responsive Hydrogel with Dynamically Reversible Rigidity Switching

To study how cells respond to dynamic mechanical changes, this research developed a light-responsive hydrogel capable of rapidly and reversibly switching between stiff and soft states. This light-responsive hydrogel is formed by cross-linking eight-arm polyethylene glycol (PEG) with photoactive yellow protein (PYP). Under blue light irradiation, the reversible conformational change of the PYP protein enables rapid, significant, and reversible modulation of the hydrogel's stiffness. By adjusting parameters such as light intensity and protein concentration, the hardness of the hydrogel can be precisely controlled, offering a broad range of tunability.

(2) Periodic Changes in Substrate Stiffness Dynamically Regulate Cellular Traction Forces

The research team used PYP hydrogels to study cellular responses to periodic changes in substrate stiffness, discovering that human mesenchymal stem cells (hMSCs) can rapidly adjust traction forces when stiffness changes. Experiments showed that cellular traction forces are closely related to the frequency of stiffness changes, with traction forces increasing under high-frequency irradiation. Different cell types exhibit varying sensitivities to stiffness changes, and dynamic stiffness changes significantly impact cellular traction forces and morphology more than static stiffness does.

(3) Long-Range Enhancement of Cellular Traction Forces is Associated with Signal Protein Accumulation

The enhancement of cellular traction forces is correlated with increased phosphorylation of FAK and Myosin IIa induced by rapid periodic changes in substrate stiffness. This phenomenon is related to both the frequency and duration of stiffness changes. The widespread accumulation of phosphorylated force-signaling proteins is directly associated with enhanced cellular traction forces.

(4) Molecular Mechanism of Force-Signaling Protein Accumulation

Research revealed that the enhancement of cellular traction forces under periodic stiffness changes correlates with the accumulation of phosphorylation levels of pFAK and pMyosin IIa. This accumulation depends on the assembly of the molecular clutch. Rapid periodic stiffness changes enable cells to re-accumulate signaling proteins, while the timing and magnitude of substrate stiffening and softening influence this accumulation process.

(5) Accumulated Signaling Proteins Promote Mechanotransduction and Traction Forces

Research indicates that accumulated pFAK likely promotes the stepwise increase in cellular traction forces by entering the cytoplasm and participating in downstream force transduction. The constructed cell model (OEpFAK hMSCs) exhibited higher traction stress, with elevated pMyosin IIa levels and enhanced co-localization with actin fibers, suggesting that increased cytoplasmic pFAK and pMyosin IIa contribute to enhanced cellular traction forces.

(6) Improved Physical Model

The research team proposed an improved molecular clutch model incorporating the FAK phosphorylation mechanism to understand force signal transduction in cells under rapid dynamic substrate stiffness changes. The model divides FAK into four states and predicts, through simulations, the impact of pFAK accumulation and dephosphorylation rates on cellular traction forces. Experiments validated the model's predictions, emphasizing the importance of dephosphorylation rates in mechanosignal transduction and revealing the influence of initial substrate stiffness on traction force increase.

(7) Downstream Mechanical Effects of Rapid Cyclic Stiffness Changes

Research shows that rapid cyclic substrate stiffness changes enhance force signal transduction in hMSCs, increase the nuclear-to-cytoplasmic ratio of YAP protein, and promote osteogenic differentiation. Furthermore, this dynamic change significantly increases cell migration speed and traction forces, indicating that cellular mechanical responses and signal transduction processes are significantly affected by dynamic substrate stiffness changes.

Conclusion and Outlook

 Cellular force signal transduction is a complex process spanning multiple time scales. Force transmission typically occurs within seconds to minutes, while the phosphorylation and dephosphorylation of signaling molecules are relatively slower. The extracellular matrix (ECM), serving as a bridge between cells and between cells and their surrounding environment, plays a crucial role in cellular force signal transduction.  

  In future research, we will further delve into simulating the impact of different mechanical force environments on the extracellular matrix. Although PYP hydrogels have achieved the fastest stiffness changes to date, biological systems may exhibit even higher-frequency periodic mechanical stimuli, exerting profound effects on cell and tissue function. By creating more advanced materials that simulate periodic mechanical stimuli in biological systems with faster response speeds, we can more accurately mimic the complex mechanical environment experienced by cells and tissues in vivo. This will help us better understand how cells convert dynamic force signals into specific biological outcomes and provide important theoretical support for the design of bioactive biomaterials and tissue engineering applications.  

  Beijing Maybio Medical Biotechnology Co., Ltd. is the world's first innovative scientific research enterprise to achieve the in vitro secretion and expression of human-derived extracellular matrix (ECM). With human cell in vitro expression technology at its core, it focuses on the R&D and application of human-derived ECM collagen protein technology, covering a business model that spans medical aesthetics, regeneration, and biomaterials.  

Our business areas encompass medical aesthetic products (collagen liquid dressings, collagen lyophilized fibers, injectable collagen gels, injectable PCL micellar gels, injectable PLLA gels, collagen efficacy skincare products), human cell-derived products (ECM raw materials), oral and maxillofacial regenerative products (silicone gel scar patches, sodium alginate oral repair gel, hemostatic sponges), as well as contract R&D and manufacturing services (OEM/ODM), among others. Currently, Tranquil Vitality is Maybio's proprietary brand. Three Tranquil Vitality ECM recombinant human collagen products have achieved commercial mass production: Tranquil Vitality No.1 focuses on repair and anti-inflammation, Tranquil Vitality No.2 targets dryness lines and fine wrinkles, and Tranquil Vitality No.3 emphasizes firming and anti-aging.  

In the future, Maybio will remain committed to translating the most cutting-edge biotechnology into practical applications, providing comprehensive, highest-quality solutions for beauty seekers, and bringing a better life to people.