Protein-Based Manufacturing (ProMan): Programming Matter through Molecular Information

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Bedewy Research Group

Protein-Based Manufacturing (ProMan): Programming Matter through Molecular Information Mostafa Bedewy Associate Professor, Director of Graduate Studies for Materials Science & Engineering Department of Mechanical Engineering and Materials Science Department of Bioengineering (secondary), Department of Chemical and Petroleum Engineering (secondary), Department of Industrial Engineering (secondary), University of Pittsburgh, PA 6/16/2026

mbedewy@pitt.edu | www.nanoproductlab.org

Our Team Sharing the ProMan Vision

Mostafa Bedewy

Won Min Park

Meng Wang

Associate Professor, Mechanical Engineering & Materials Science, University of Pittsburgh

Associate Professor, Chemical Engineering, Kansas State University

Associate Professor, Civil and Environmental Engineering, University of Houston 2

Protein-Based Manufacturing: Programming Matter Through Molecular Information Conventional Manufacturing

Protein-Based Manufacturing Amino acid sequence

0.54 nm

11 nm

Mechanical Force

Thermal/ Optical Energy

CAD  Digital Tool Path

Hierarchically structured macroscopic material

Folding and assembly

Can manufacturing move from shaping matter with energy to programming matter with information?

Blue Sky: bring sequence-guided structure into the digital industrial age 3

Every Manufacturing Era Begins with a New Way to Control Matter Bronze age

Iron age

Modern age Steel Polymers Semiconductors

New manufacturing

Stone age

Composites

SequenceProgrammed Materials Let’s grab that rock and shape it

We can melt copper, tin, etc.

Look! We can even forge iron

We design the materials structure

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Without manufacturing, we’d all still be stuck with…

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The Polymer Lesson: A New Material Class Creates a New Manufacturing Ecosystem Metal era: mass production of shaped metal assemblies

Polymer era: lightweight, molded, multifunctional components

Protein-enabled future?

Fibers

Sponges Freeze drying

Dry/wet spinning, Electrospinning A

B

100 µm

5 µm

Films Casting, Spin coating, Dip coating

Microspheres

RSF solution

F

Electro-spraying

C

1 mm

D

E

1 mm

Tubes

1953 Chevrolet Corvette

2026 Chevrolet Corvette

Metals shaped by controlling force/heat

Polymers shaped by rheology/molding

Dipping, gel spinning

5 µm

Hydrogels Sonication, electric current, pH change

Bedewy et al., 2021 Proteins structured by sequence/assembly

Each new material class required new processes, machines, design rules, & expertise. Protein  new manufacturing ecosystem.

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The Silk Lesson: We Manufactured the Product BUT Nature Manufactured the Structure Silk is a macroscopic protein product

Who made what?

Humans did: • grew leaves • fed the worm • harvest • clean/degum • spin/weave • dye • cut/sew

Nature did: • sequence • folding • β-sheet assembly • hierarchical fiber formation • toughness / flexibility

What ProMan changes?

Sequence

Fold

Bind

Catalyze`

Assemble

template

We made the tie; silkworm made the architecture Protein-Based Manufacturing = Sequence Programming + Process Control

From organism-driven materials  digitally controlled manufacturing

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Natural Silk Structure

This is why silk is a great material

www.bedewygroup.com

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The tetrahedron gets a new input FROM: Understanding the causal relationship (cause and effect)

PROCESS – STRUCTURE – PROPERTY – PERFORMANCE Material design based on a predetermined goal

TO: Understanding the causal relationship (cause and effect)

SEQUENCE – PROCESS – STRUCTURE – PROPERTY – PERFORMANCE Material design based on a predetermined goal

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Why proteins?

Superheroes of biopolymers

1A

1 nm

10 nm

100 nm

1 mm

Adapted from the Paul Scherrer Institut website (http://www.psi.ch)

1. DIVERSITY: Huge diversity of shape, sizes and properties of proteins 2. SIZE: Sub-20-nm range, nanofabricated structures approach proteins 3. SCALABILITY: Economic and sustainable mass production of protein 10

Diversity of proteins

 Human proteome contains about 20,000 distinct proteins.1  It’s likely that there are more than 10 billion different proteins in existence.2  Proteins come in various sizes and shapes. 3 [1] Wilhelm et al. Nature, 2014.

[2] Koonin EV, Galperin MY. Sequence - Evolution - Function: Computational Approaches in Comparative Genomics. Boston: Kluwer Academic; 2003.

[3] Alberts et al., “Molecular Biology of the Cell,” 5th edition.

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Examples of engineered proteins: design for assembly Protein Origami

2D Crystals

20 nm Gradišar et al., Nat. Chem. Biol. 2013 Lanci et al., PNAS, 2011

Ohno and Inoue, ACS Nano, 2015

Gonen et al., Science, 2015

“Non-engineered proteins” form 2D patterns Hydrophobins

S-layers

Scheuring et al., Mol. Microbiol, 2002

Yamasaki et al., ACS Nano, 2016

Chung et al., PNAS, 2010

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The Grand Challenges Ahead Sequence Design  Predict manufacturable protein sequences, not just stable structures.

Assembly Control  Control placement, orientation, registration, and defect density.

Functional Transfer  Translate protein patterns into metals, oxides, semiconductors, catalysts, and devices.

Manufacturing Scale-Up  Build scalable expression, purification, shaping, inline metrology, and quality control.

Community Infrastructure  Create testbeds, standards, datasets, centers, curricula, and killer applications.

A Manufacturing Frontier Requires a Community: • Manufacturing engineers • Protein designers • Synthetic biologists • Chemical engineers • Materials scientists • AI/autonomy researchers • Metrologists • Sustainability/TEA experts • Industry/government

Let’s build the protein foundry! 14

The Protein Foundry

Digital Design

AI Protein Design

Bioreactor

Purification

Assembly/ Processing

Inline Metrology

Product

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