thumbnail_TIRELLI-chiaro-2.png

TIRELLI-chiaro-2.png

Our muscles – be them voluntary such as our skeletal muscles, or involuntary such as those lining our blood vessels – contract, and relax, all the time. These are reversible, cell-mediated processes; when a contracted muscle does not revert to its relaxed state, e.g. because excessively frequent stimulation by motor neurons, pathological situations arise, for example cramps (physiological tetanus).
In our bodies, we also experience a second form of cell-mediated contraction, which is both (much) slower and irreversible. This happens e.g. when a scar matures (becoming smaller but harder) or when a foreign body is encapsulated in a fibrotic tissue (think at breast implants). In order to differentiate this from the rapid and reversible contraction of muscles, these slower and irreversible processes are referred to as contractures. 

Although necessary to firmly close a wound, contractures are not exactly welcome. If cells (typically fibroblasts; or a related, more contractile phenotype called myofibroblasts) contract a matrix, they do not only change its dimensions; the construct becomes denser and thus harder, and mobility and overall survival of cells within may be an issue, partially because of physical hindrance, partially because of the lower diffusion of nutrients and oxygen. In anti-scarring therapies, or in tissue engineering/regenerative medicine, it would be beneficial to develop conditions that minimize contracture; in vitro tests that can accurately predict contracture behaviour are therefore useful.  

However, there may be more one kind of contracture. 

In a [recent paper from our group](https://www.sciencedirect.com/science/article/pii/S0928493122000212?via%3Dihub), we have reflected that the contracture of a wound (cells contracting it from within; 3D contracture) and the formation of a contracted fibrotic tissue around an implant (cells contracting the interface with the material; 2D contracture) may be geometrically and probably also functionally different processes. In this study, we have developed model systems for both the 2D and 3D contracture. We employed fibrin with variable modulus (Figure 1A), axially anchoring them (Figure 1B) and seeding cells within or on the top of them (Figure 1C). Cells contracted these matrices by pulling fibrils (Figure 2), and the speed of contracture [was always inversely proportional to their stiffness](https://ars.els-cdn.com/content/image/1-s2.0-S0928493122000212-mmc2.mp4) and directly proportional to the presence of fibrotic agents [such as TGF-b1](https://ars.els-cdn.com/content/image/1-s2.0-S0928493122000212-mmc3.mp4); however, while cells seeded inside shrank fibrin in a 3D contracture, those on the surface bent the materials without migrating into them, in a form of 2D contracture. The two processes were not only geometrically, but also functionally different: for example, fibroblasts were more likely to differentiate into myofibroblasts in 3D contracture, but they oriented along the contracture axis much more in 2D contracture. 

Finally, we have demonstrated that dystrophic muscle cells have a propensity to 3D (but not 2D) contracture, similar to fibroblasts but different from healthy or genetically corrected muscle cells, which may at least partially explain the fibrotic evolution of muscle in Duchenne’s dystrophy.

![Schermata 2022-05-09 alle 18.58.37.png](https://res.cloudinary.com/milan-polymer-days/image/upload/v1652115579/Schermata_2022_05_09_alle_18_58_37_343e449d65.png)

**Figure 1**. A. Young’s and storage shear modulus of fibrin with different concentrations. B. Scheme of how fibrin constructs are axially anchored. C. Pictorial explanation of the different contracture modes following 2D (on the top) and 3D (within fibrin) cell seeding in axially anchored fibrin matrices.

![Schermata 2022-05-09 alle 19.00.04.png](https://res.cloudinary.com/milan-polymer-days/image/upload/v1652115630/Schermata_2022_05_09_alle_19_00_04_8e217a2ee4.png)

**Figure 2**. SEM pictures of fibroblasts pulling fibrin fibrillar networks

![Schermata 2022-05-09 alle 19.00.51.png](https://res.cloudinary.com/milan-polymer-days/image/upload/v1652115681/Schermata_2022_05_09_alle_19_00_51_a99e2237f4.png)

**Figure 3**. the reduction of cross-sectional area with time is a measure of contracture kinetics. Fibrin 3D-seeded with dystrophic myoblasts (DYS) contract with a kinetics similar to that of 3D-seeded fibroblasts (HDFa), significantly more rapid than healthy (WT) or genetically corrected dystrophic myoblasts (DYS-CORR).

Whether we consciously realize it or not, we are all familiar with biological contraction phenomena.

large_Schermata 2022-05-09 alle 18.58.19.png

medium_Schermata 2022-05-09 alle 18.58.19.png

small_Schermata 2022-05-09 alle 18.58.19.png

thumbnail_Schermata 2022-05-09 alle 18.58.19.png

Schermata 2022-05-09 alle 18.58.19.png

Cells contracting materials

medium_unnamed.jpg

small_unnamed.jpg

thumbnail_unnamed.jpg

unnamed.jpg

thumbnail_RAFFAINI-chiaro-2.png

RAFFAINI-chiaro-2.png

This paper reports on synthesis, acid–base properties, and self-structuring in water of a chiral polyamidoamino acid, M-*l*-Gln, obtained from the polyaddition of *N*,*N*′-methylenebisacrylamide with *l*-glutamine, with the potential of establishing hydrogen bonds through its prim-amide pendants. The M-*l*-Gln showed pH-responsive circular dichroism spectra, revealing ordered conformations. Structuring was nearly insensitive to ionic strength but sensitive to denaturing agents. The NMR diffusion studies were consistent with a population of unimolecular nanoparticles thus excluding aggregation. The M-*l*-Gln had the highest molecular weight and hydrodynamic radius among all polyamidoamino acids described. Possibly, transient hydrogen bonds between l-glutamine molecules and M-*l*-Gln growing chains facilitated the polyaddition reaction. Theoretical modeling showed that M-*l*-Gln assumed pH-dependent self-ordered coil conformations with main chain transoid arrangements reminiscent of the protein hairpin motif owing to intramolecular dipole moments and hydrogen bonds. The latter were most numerous at the isoelectric point (pH 4.5), where they mainly involved even topologically distant main chain amide N–H and side chain amide C=O brought to proximity by structuring. Hydrogen bonds at pH 4.5 were also suggested by variable temperature NMR. The 2D NOESY experiments at pH 4.5 confirmed the formation of compact structures through the analysis of the main chain/side chain hydrogen contacts, in line with MD simulations. [View Full-Text](https://www.mdpi.com/2073-4360/12/4/881/htm).

large_Schermata 2022-05-04 alle 18.17.45.png

medium_Schermata 2022-05-04 alle 18.17.45.png

small_Schermata 2022-05-04 alle 18.17.45.png

thumbnail_Schermata 2022-05-04 alle 18.17.45.png

Schermata 2022-05-04 alle 18.17.45.png

Hydrogen Bonding in a l-Glutamine-Based Polyamidoamino Acid and its pH-Dependent Self-Ordered Coil Conformation

thumbnail_MIPOL-blog.png

MIPOL-blog.png

The organizing committee of the Milan Polymer Days international congress - MIPOL2022 will support the participation of Ukrainian scientists, even if they are temporarily living abroad, from all research institutions in the war-affected Ukrainian regions, by accepting remote poster communications free of charge.

In order to participate in the MIPOL2022 congress, the interested scientists are invited to submit a regular abstract following the procedures indicated in the[ relevant congress webpage](https://www.milanpolymerdays.org/congress/call-for-abstracts). 

Abstracts will be evaluated by the scientific committee in real time and, if accepted, included in the congress program and booklet. A slot will be subsequently allocated for the general poster discussion that will take place on June 19th through the [MS-TEAMS platform](https://www.milanpolymerdays.org/congress/mipol-in-a-nutshell). 

The Organizing Committee will provide young scientists with relevant information for participating in the poster award competition.

For any queries, please do not hesitate to contact us via our e-mail address **mipol@unimi.it**.

MIPOL2022 will support the participation of Ukrainian scientists.

large_ucrainamipol.png

medium_ucrainamipol.png

small_ucrainamipol.png

thumbnail_ucrainamipol.png

ucrainamipol.png

Our commitment to help Ukrainian scientists

La conservazione ed il restauro dei beni culturali, con particolare riguardo al patrimonio archeologico, artistico, archivistico, librario, musicale, teatrale e cinematografico di cui l’Italia è ricca, richiede conoscenze e competenze storico-umanistiche e scientifiche.
Relativamente ai materiali da costruzione, gli edifici venivano storicamente costruiti utilizzando pietra naturale, con un uso prevalente di materiali locali. Tali materiali erano soggetti a deterioramento chimico, dovuto a corrosione o erosione superficiali dovute all’azione di agenti atmosferici o deterioramento biologico legato ad esempio alla formazione di biofilm. Quali sono quindi i materiali per il consolidamento e la protezione normalmente utilizzati nel restauro dei beni architettonici? Quali i requisiti che essi devono soddisfare? Partendo dai materiali naturali, fino ai polimeri sintetici e poi ancora ai nanomateriali il progredire delle conoscenze ha messo a disposizione strumenti di protezione e conservazione sempre più efficienti.


Talking with the scientist: incontro online con la Prof.ssa Lucia Toniolo (Politecnico di Milano) e la Prof.ssa Paola Fermo, (Università di Milano).

large_276317169_1659678891045491_2050426791891128150_n.jpeg

medium_276317169_1659678891045491_2050426791891128150_n.jpeg

small_276317169_1659678891045491_2050426791891128150_n.jpeg

thumbnail_276317169_1659678891045491_2050426791891128150_n.jpeg

276317169_1659678891045491_2050426791891128150_n.jpeg

VIDEO - Materiali avanzati per la conservazione della pietra nell'architettura storica

about us

congress

blog

contacts

sign up

milan

polymer

days

milan polymer days

Don't miss our blog

May 9th 22

Cells contracting materials

Nicola Tirelli

May 4th 22

Hydrogen Bonding in a l-Glutamine-Based Polyamidoamino Acid and its pH-Dependent Self-Ordered Coil Conformation

MDPI Publisher of Open Access Journals, Giuseppina Raffaini

May 4th 22

Our commitment to help Ukrainian scientists

MIPOL GROUP

Apr 7th 22

VIDEO - Materiali avanzati per la conservazione della pietra nell'architettura storica

MIPOL GROUP

Subscribe to our newsletter