Farid Alisafaei
@faridalisafaei.bsky.social
Assistant Professor of Mechanical Engineering @njit.bsky.social
————————————————————
PI, MechanoBiology and BioMechanics (MBBM) Lab http://www.mbbm-lab.com
————————————————————
Former NIH Postdoc @upenn.bsky.social
————————————————————
PI, MechanoBiology and BioMechanics (MBBM) Lab http://www.mbbm-lab.com
————————————————————
Former NIH Postdoc @upenn.bsky.social
1️⃣ 1️⃣ Without Microtubules, Direction Does Not Matter!
With disruption of microtubules, our theoretical model showed that fibroblasts behaved just as classical models predicted—responding only to stress magnitude, not direction!
With disruption of microtubules, our theoretical model showed that fibroblasts behaved just as classical models predicted—responding only to stress magnitude, not direction!
March 25, 2025 at 6:52 PM
1️⃣ 1️⃣ Without Microtubules, Direction Does Not Matter!
With disruption of microtubules, our theoretical model showed that fibroblasts behaved just as classical models predicted—responding only to stress magnitude, not direction!
With disruption of microtubules, our theoretical model showed that fibroblasts behaved just as classical models predicted—responding only to stress magnitude, not direction!
🔟 Classical Cell Models Fall Short
However, classical theoretical models failed:
Classical models = stress magnitude matters most
Our model = stress anisotropy is the real driver!
However, classical theoretical models failed:
Classical models = stress magnitude matters most
Our model = stress anisotropy is the real driver!
March 25, 2025 at 6:52 PM
🔟 Classical Cell Models Fall Short
However, classical theoretical models failed:
Classical models = stress magnitude matters most
Our model = stress anisotropy is the real driver!
However, classical theoretical models failed:
Classical models = stress magnitude matters most
Our model = stress anisotropy is the real driver!
9️⃣ Model Prediction:
Our theoretical model predicted and explained fibroblast activation under tension:
When stress was isotropic, fibroblasts stayed inactive.
When stress was anisotropic, activation skyrocketed!
Our theoretical model predicted and explained fibroblast activation under tension:
When stress was isotropic, fibroblasts stayed inactive.
When stress was anisotropic, activation skyrocketed!
March 25, 2025 at 6:52 PM
9️⃣ Model Prediction:
Our theoretical model predicted and explained fibroblast activation under tension:
When stress was isotropic, fibroblasts stayed inactive.
When stress was anisotropic, activation skyrocketed!
Our theoretical model predicted and explained fibroblast activation under tension:
When stress was isotropic, fibroblasts stayed inactive.
When stress was anisotropic, activation skyrocketed!
8️⃣ Microtubules: The Missing Piece in Tension Sensing?
When we disrupted microtubules, fibroblasts responded in the opposite way—they activated more under isotropic tension instead of anisotropic tension! This means microtubules are crucial for cells to sense and respond to tension anisotropy
When we disrupted microtubules, fibroblasts responded in the opposite way—they activated more under isotropic tension instead of anisotropic tension! This means microtubules are crucial for cells to sense and respond to tension anisotropy
March 25, 2025 at 6:52 PM
8️⃣ Microtubules: The Missing Piece in Tension Sensing?
When we disrupted microtubules, fibroblasts responded in the opposite way—they activated more under isotropic tension instead of anisotropic tension! This means microtubules are crucial for cells to sense and respond to tension anisotropy
When we disrupted microtubules, fibroblasts responded in the opposite way—they activated more under isotropic tension instead of anisotropic tension! This means microtubules are crucial for cells to sense and respond to tension anisotropy
7️⃣ Fibroblasts in the Skin: A Natural Example
Why is this exciting? Because in tissues like skin, fibroblasts experience anisotropic tension due to collagen alignment along Langer’s lines. By modulating tension direction, we may be able to control fibroblast activation!
Why is this exciting? Because in tissues like skin, fibroblasts experience anisotropic tension due to collagen alignment along Langer’s lines. By modulating tension direction, we may be able to control fibroblast activation!
March 25, 2025 at 6:52 PM
7️⃣ Fibroblasts in the Skin: A Natural Example
Why is this exciting? Because in tissues like skin, fibroblasts experience anisotropic tension due to collagen alignment along Langer’s lines. By modulating tension direction, we may be able to control fibroblast activation!
Why is this exciting? Because in tissues like skin, fibroblasts experience anisotropic tension due to collagen alignment along Langer’s lines. By modulating tension direction, we may be able to control fibroblast activation!
6️⃣ Tension Anisotropy vs. ECM Stiffness:
Which has a bigger impact on fibroblast activation?
We found that tension anisotropy is more important than ECM stiffness! On soft matrices, anisotropic tension activated fibroblasts more than stiff isotropic environments.
Which has a bigger impact on fibroblast activation?
We found that tension anisotropy is more important than ECM stiffness! On soft matrices, anisotropic tension activated fibroblasts more than stiff isotropic environments.
March 25, 2025 at 6:52 PM
6️⃣ Tension Anisotropy vs. ECM Stiffness:
Which has a bigger impact on fibroblast activation?
We found that tension anisotropy is more important than ECM stiffness! On soft matrices, anisotropic tension activated fibroblasts more than stiff isotropic environments.
Which has a bigger impact on fibroblast activation?
We found that tension anisotropy is more important than ECM stiffness! On soft matrices, anisotropic tension activated fibroblasts more than stiff isotropic environments.
5️⃣ Breaking the Loop Stops Activation:
Disrupting this feedback loop—by reducing tension anisotropy or inhibiting protrusions—stopped fibroblasts from activating. This suggests that fibrosis and wound healing could be controlled by tuning stress anisotropy!
Disrupting this feedback loop—by reducing tension anisotropy or inhibiting protrusions—stopped fibroblasts from activating. This suggests that fibrosis and wound healing could be controlled by tuning stress anisotropy!
March 25, 2025 at 6:52 PM
5️⃣ Breaking the Loop Stops Activation:
Disrupting this feedback loop—by reducing tension anisotropy or inhibiting protrusions—stopped fibroblasts from activating. This suggests that fibrosis and wound healing could be controlled by tuning stress anisotropy!
Disrupting this feedback loop—by reducing tension anisotropy or inhibiting protrusions—stopped fibroblasts from activating. This suggests that fibrosis and wound healing could be controlled by tuning stress anisotropy!
4️⃣ The Self-Reinforcing Loop:
We saw that fibroblasts extend protrusions that interact with collagen fibers. This sets up a self-reinforcing loop:
💠 Protrusions align collagen fibers
💠 Aligned fibers stabilize and strengthen protrusions
💠 This amplifies tension in one direction
We saw that fibroblasts extend protrusions that interact with collagen fibers. This sets up a self-reinforcing loop:
💠 Protrusions align collagen fibers
💠 Aligned fibers stabilize and strengthen protrusions
💠 This amplifies tension in one direction
March 25, 2025 at 6:52 PM
4️⃣ The Self-Reinforcing Loop:
We saw that fibroblasts extend protrusions that interact with collagen fibers. This sets up a self-reinforcing loop:
💠 Protrusions align collagen fibers
💠 Aligned fibers stabilize and strengthen protrusions
💠 This amplifies tension in one direction
We saw that fibroblasts extend protrusions that interact with collagen fibers. This sets up a self-reinforcing loop:
💠 Protrusions align collagen fibers
💠 Aligned fibers stabilize and strengthen protrusions
💠 This amplifies tension in one direction
3️⃣ Why Does This Matter?
This transformation is essential for wound healing—but if it goes unchecked, it can lead to excessive scarring and fibrocontractile diseases like fibrosis. Fibrosis not only impairs tissue function but can also promote skin cancer invasion.
This transformation is essential for wound healing—but if it goes unchecked, it can lead to excessive scarring and fibrocontractile diseases like fibrosis. Fibrosis not only impairs tissue function but can also promote skin cancer invasion.
March 25, 2025 at 6:52 PM
3️⃣ Why Does This Matter?
This transformation is essential for wound healing—but if it goes unchecked, it can lead to excessive scarring and fibrocontractile diseases like fibrosis. Fibrosis not only impairs tissue function but can also promote skin cancer invasion.
This transformation is essential for wound healing—but if it goes unchecked, it can lead to excessive scarring and fibrocontractile diseases like fibrosis. Fibrosis not only impairs tissue function but can also promote skin cancer invasion.
2️⃣ Tension Anisotropy: A New Activation Factor
We found that when fibroblasts experience higher tension in one direction, they activate into highly contractile myofibroblasts.
We found that when fibroblasts experience higher tension in one direction, they activate into highly contractile myofibroblasts.
March 25, 2025 at 6:52 PM
2️⃣ Tension Anisotropy: A New Activation Factor
We found that when fibroblasts experience higher tension in one direction, they activate into highly contractile myofibroblasts.
We found that when fibroblasts experience higher tension in one direction, they activate into highly contractile myofibroblasts.
March 22, 2025 at 2:12 AM
5️⃣ The opportunity: By controlling mechanical conditions, we can optimize fibroblast memory, leading to better graft integration, less scarring, and improved wound healing.
March 22, 2025 at 2:12 AM
5️⃣ The opportunity: By controlling mechanical conditions, we can optimize fibroblast memory, leading to better graft integration, less scarring, and improved wound healing.
4️⃣ Why does this matter? In skin grafting for burns and chronic wounds, skin grafts are mechanically stretched before transplantation. How they are stretched determines whether they heal properly or lead to scarring and graft failure.
March 22, 2025 at 2:12 AM
4️⃣ Why does this matter? In skin grafting for burns and chronic wounds, skin grafts are mechanically stretched before transplantation. How they are stretched determines whether they heal properly or lead to scarring and graft failure.
3️⃣ Our discovery: Fibroblasts in 3D tissues subjected to static mechanical stretching for extended periods retain a memory of the stretch—remaining activated long after the strain is gone.
March 22, 2025 at 2:12 AM
3️⃣ Our discovery: Fibroblasts in 3D tissues subjected to static mechanical stretching for extended periods retain a memory of the stretch—remaining activated long after the strain is gone.
2️⃣ What we know: Fibroblasts adjust their behavior in response to mechanical forces. But what happens when those forces are removed?
March 22, 2025 at 2:12 AM
2️⃣ What we know: Fibroblasts adjust their behavior in response to mechanical forces. But what happens when those forces are removed?
(8)📖Curious to learn more?
Read our full paper in Acta Biomaterialia for free access until Jan 18, 2025:
🔗 authors.elsevier.com/a/1kB0g6CFjZ...
Read our full paper in Acta Biomaterialia for free access until Jan 18, 2025:
🔗 authors.elsevier.com/a/1kB0g6CFjZ...
authors.elsevier.com
December 3, 2024 at 1:58 PM
(8)📖Curious to learn more?
Read our full paper in Acta Biomaterialia for free access until Jan 18, 2025:
🔗 authors.elsevier.com/a/1kB0g6CFjZ...
Read our full paper in Acta Biomaterialia for free access until Jan 18, 2025:
🔗 authors.elsevier.com/a/1kB0g6CFjZ...
(7)🔍A key prediction:
Our model predicts that surgeons stop expanding the graft when the two limits diverge.
✅ We compared these predictions with extensive experimental data from surgeries and validated their accuracy across different meshing ratios and donor skin sizes.
Our model predicts that surgeons stop expanding the graft when the two limits diverge.
✅ We compared these predictions with extensive experimental data from surgeries and validated their accuracy across different meshing ratios and donor skin sizes.
December 3, 2024 at 1:58 PM
(7)🔍A key prediction:
Our model predicts that surgeons stop expanding the graft when the two limits diverge.
✅ We compared these predictions with extensive experimental data from surgeries and validated their accuracy across different meshing ratios and donor skin sizes.
Our model predicts that surgeons stop expanding the graft when the two limits diverge.
✅ We compared these predictions with extensive experimental data from surgeries and validated their accuracy across different meshing ratios and donor skin sizes.
(6)🚀Our solution:
We developed a model that uncovers the mechanisms behind skin graft expansion. It captures two key factors involved in skin graft expansion:
1️⃣ Rotation of incision arms
2️⃣ Stretching of the skin
The model provides upper and lower limits for graft expansion.
We developed a model that uncovers the mechanisms behind skin graft expansion. It captures two key factors involved in skin graft expansion:
1️⃣ Rotation of incision arms
2️⃣ Stretching of the skin
The model provides upper and lower limits for graft expansion.
December 3, 2024 at 1:58 PM
(6)🚀Our solution:
We developed a model that uncovers the mechanisms behind skin graft expansion. It captures two key factors involved in skin graft expansion:
1️⃣ Rotation of incision arms
2️⃣ Stretching of the skin
The model provides upper and lower limits for graft expansion.
We developed a model that uncovers the mechanisms behind skin graft expansion. It captures two key factors involved in skin graft expansion:
1️⃣ Rotation of incision arms
2️⃣ Stretching of the skin
The model provides upper and lower limits for graft expansion.
(5) This overestimation persists across experience levels. Survey data shows no significant difference between estimates from senior surgeons and residents. A better model is essential to improve accuracy and outcomes.
pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov/articles/PMC...
The real expansion rate of meshers and micrografts: things we should keep in mind
Skin graft expansion techniques (mesh and micrograft) are widely used, but there is ample evidence that skin graft meshers do not provide their claimed expansion rates. Although this finding might not...
pmc.ncbi.nlm.nih.gov
December 3, 2024 at 1:58 PM
(5) This overestimation persists across experience levels. Survey data shows no significant difference between estimates from senior surgeons and residents. A better model is essential to improve accuracy and outcomes.
pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov/articles/PMC...
(4) Surgeons widely recognize that actual skin graft expansions often fall short of predictions made by the conventional model. Despite this, they overestimate these ratios by 55%, showing a clear need for a more accurate and practical predictive model.
pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov/articles/PMC...
The real expansion rate of meshers and micrografts: things we should keep in mind
Skin graft expansion techniques (mesh and micrograft) are widely used, but there is ample evidence that skin graft meshers do not provide their claimed expansion rates. Although this finding might not...
pmc.ncbi.nlm.nih.gov
December 3, 2024 at 1:58 PM
(4) Surgeons widely recognize that actual skin graft expansions often fall short of predictions made by the conventional model. Despite this, they overestimate these ratios by 55%, showing a clear need for a more accurate and practical predictive model.
pmc.ncbi.nlm.nih.gov/articles/PMC...
pmc.ncbi.nlm.nih.gov/articles/PMC...